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1

Pranata, Kadek Dwipayana, I. Gede Putu Wirawan, I. Putu Agus Hendra Wibawa, I. Ketut Suada, I. Nyoman Wijaya, and Trisna Agung Phabiola. "ANTIFUNGAL ACTIVITY OF SIAM CITRUS (Citrus nobilis L.) ESSENTIAL OIL AGAINTS Lasiodiplodia theobromae THE PATHOGEN OF BLENDOK DISEASE." International Journal of Biosciences and Biotechnology 11, no. 2 (April 30, 2024): 61. http://dx.doi.org/10.24843/ijbb.2024.v11.i02.p08.

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Siam citrus (C. nobilis L.) is a type of citrus that is most widely cultivated in Bangli Regency. The main disease that attacks citrus plants is blendok caused by the fungus L. theobromae. Based on research siam citrus peel contains essensial oils that have potential as antifungals. The aim of this study was to study chemical content of essensial oil from siam citrus peel and its activity as an antifungal againts L. theobromae. Essensial oil was destilled using hydro steam distillition and analyzed by means of GC-MS. Antifungal activiy testing was carried out using the agar-well diffusion method with concentrations of 1%, 10%, 25%, 50%, 75%, and 100%. Dithane M45 6 g/l and DMSO 10% were used as positive and negative controls. The results showed that the siam citrus peel from Kintamani, Bangli contains essensial oils with the main chemical components, i.e. D-limonene (57.26%), Beta-pinene (9.09%), and Beta-myrcene (4.03%) which has uses as an antifungal, additive, antitumor, asthma and allergy reliever, repellent, anti-inflammatory, antioxidant, anticancer, and antibacterial. Essential oil concentration of 25 to 100% can inhibit the growth of L. theobromae. The largest diameter of inhibition is shown at a concentration of 100% and the smallest diameter of inhibition is shown at a concentration of 25%. Keywords: C. nobilis L., essensial oils, GC-MS, L. Theobromae, antifungal
2

Andrade, B. S., R. Matias, B. O. Corrêa, A. K. M. Oliveira, D. G. F. Guidolin, and A. R. Roel. "Phytochemistry, antioxidant potential and antifungal of Byrsonima crassifolia on soil phytopathogen control." Brazilian Journal of Biology 78, no. 1 (July 10, 2017): 140–46. http://dx.doi.org/10.1590/1519-6984.166532.

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Abstract The use of chemical defensives to control fungal diseases has by consequence to impact negatively over the environment and human health, this way, the use of plant extracts with antifungal properties along with proper cultural management makes viable an alternative plant production control, specially for familiar and organic cultures. The objective of this study was to perform phytochemical and antioxidant analysis of Byrsonima crassifolia (canjiqueira) barks and evaluate its antifungal potential over Fusarium solani and Sclerotinia sclerotiorum mycelial growth. The ethanol extract from plants collected in Pantanal, Mato Grosso do Sul, Brazil was submitted to phytochemical prospection, total phenol and flavonoids quantification and antioxidant activiy determination (DPPH). To evaluate antifungal activity concentrations of 800, 1200, 1600, 2000 and 2400 µg 100 mL-1 of ethanol extract were used. Which concentration was separately incorporated in agar (PDA) and shed in Petri dishes, followed by the fungi mycelial disc where the colonies diameter was measured daily. Negatives control with agar without extract and agar with an ethanol solution were used. The B. crassifolia ethanol extract presented inhibitory activity over the fungi studied where concentrations of 800 and 1600 µg 100 mL-1, inhibited 38% of the mycelial growth of F. solani; to S. sclerotiorum the best concentration was 2400 µg 100 mL1, reducing 37.5%. The antifungal bark extract potential of this specie is attributed to phenolic compounds and to triterpenes derivatives.
3

Vahedi-Shahandashti, Roya, and Cornelia Lass-Flörl. "Novel Antifungal Agents and Their Activity against Aspergillus Species." Journal of Fungi 6, no. 4 (October 9, 2020): 213. http://dx.doi.org/10.3390/jof6040213.

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There is a need for new antifungal agents, mainly due to increased incidence of invasive fungal infections (IFI), high frequency of associated morbidity and mortality and limitations of the current antifungal agents (e.g., toxicity, drug–drug interactions, and resistance). The clinically available antifungals for IFI are restricted to four main classes: polyenes, flucytosine, triazoles, and echinocandins. Several antifungals are hampered by multiple resistance mechanisms being present in fungi. Consequently, novel antifungal agents with new targets and modified chemical structures are required to combat fungal infections. This review will describe novel antifungals, with a focus on the Aspergillus species.
4

Bouz, Ghada, and Martin Doležal. "Advances in Antifungal Drug Development: An Up-To-Date Mini Review." Pharmaceuticals 14, no. 12 (December 16, 2021): 1312. http://dx.doi.org/10.3390/ph14121312.

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The utility of clinically available antifungals is limited by their narrow spectrum of activity, high toxicity, and emerging resistance. Antifungal drug discovery has always been a challenging area, since fungi and their human host are eukaryotes, making it difficult to identify unique targets for antifungals. Novel antifungals in clinical development include first-in-class agents, new structures for an established target, and formulation modifications to marketed antifungals, in addition to repurposed agents. Membrane interacting peptides and aromatherapy are gaining increased attention in the field. Immunotherapy is another promising treatment option, with antifungal antibodies advancing into clinical trials. Novel targets for antifungal therapy are also being discovered, allowing the design of new promising agents that may overcome the resistance issue. In this mini review, we will summarize the current status of antifungal drug pipelines in clinical stages, and the most recent advancements in preclinical antifungal drug development, with special focus on their chemistry.
5

Burger-Kentischer, Anke, Doris Finkelmeier, Petra Keller, Jörg Bauer, Holger Eickhoff, Gerald Kleymann, Walid Abu Rayyan, et al. "A Screening Assay Based on Host-Pathogen Interaction Models Identifies a Set of Novel Antifungal Benzimidazole Derivatives." Antimicrobial Agents and Chemotherapy 55, no. 10 (July 11, 2011): 4789–801. http://dx.doi.org/10.1128/aac.01657-10.

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ABSTRACTFungal infections are a serious health problem in clinics, especially in the immune-compromised patient. Disease ranges from widespread superficial infections like vulvovaginal infections to life-threatening systemic candidiasis. Especially for systemic mycoses, only a limited arsenal of antifungals is available. The most commonly used classes of antifungal compounds used include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapy, significant side effects, and high costs for several antifungals, there is a medical need for new antifungals in the clinic and general practice. In order to expand the arsenal of compounds with antifungal activities, we screened a compound library including more than 35,000 individual compounds derived from organic synthesis as well as combinatorial compound collections representing mixtures of compounds for antimycotic activity. In total, more than 100,000 compounds were screened using a new type of activity-selectivity assay, analyzing both the antifungal activity and the compatibility with human cells at the same time. One promising hit, an (S)-2-aminoalkyl benzimidazole derivative, was developed among a series of lead compounds showing potent antifungal activity. (S)-2-(1-Aminoisobutyl)-1-(3-chlorobenzyl) benzimidazole showed the highest antifungal activity and the best compatibility with human cells in several cell culture models and against a number of clinical isolates of several species of pathogenicCandidayeasts. Transcriptional profiling indicates that the newly discovered compound is a potential inhibitor of the ergosterol pathway, in contrast to other benzimidazole derivatives, which target microtubules.
6

Klochenko, Peter D., Irina A. Elanskaya, Tatyana F. Shevchenko, and Elena V. Sokolova. "Antifungal activity of freshwater cyanobacteria." Algological Studies/Archiv für Hydrobiologie, Supplement Volumes 103 (December 3, 2001): 143–49. http://dx.doi.org/10.1127/algol_stud/103/2001/143.

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7

Wiederhold, Nathan P. "Pharmacodynamics, Mechanisms of Action and Resistance, and Spectrum of Activity of New Antifungal Agents." Journal of Fungi 8, no. 8 (August 16, 2022): 857. http://dx.doi.org/10.3390/jof8080857.

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Several new antifungals are currently in late-stage development, including those with novel pharmacodynamics/mechanisms of action that represent new antifungal classes (manogepix, olorofim, ATI-2307, GR-2397). Others include new agents within established classes or with mechanisms of action similar to clinically available antifungals (ibrexafungerp, rezafungin, oteseconazole, opelconazole, MAT2203) that have been modified in order to improve certain characteristics, including enhanced pharmacokinetics and greater specificity for fungal targets. Many of the antifungals under development also have activity against Candida and Aspergillus strains that have reduced susceptibility or acquired resistance to azoles and echinocandins, whereas others demonstrate activity against species that are intrinsically resistant to most clinically available antifungals. The tolerability and drug–drug interaction profiles of these new agents also appear to be promising, although the number of human subjects that have been exposed to many of these agents remains relatively small. Overall, these agents have the potential for expanding our antifungal armamentarium and improving clinical outcomes in patients with invasive mycoses.
8

Lemriss, S., F. Laurent, A. Couble, E. Casoli, J. M. Lancelin, D. Saintpierre-Bonaccio, S. Rifai, A. Fassouane, and P. Boiron. "Screening of nonpolyenic antifungal metabolites produced by clinical isolates of actinomycetes." Canadian Journal of Microbiology 49, no. 11 (November 1, 2003): 669–74. http://dx.doi.org/10.1139/w03-088.

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The purpose of this work was to screen clinical isolates of actinomycetes producing nonpolyenic antifungals. This choice was made to limit the problem of rediscovery of well-known antifungal families, especially polyenic antifungals. One hundred and ten strains were tested, using two diffusion methods and two test media, against three yeast species and three filamentous fungi. Among 54 strains (49%) showing antifungal activity, five strains belonging to the genus Streptomyces were active against all test organisms and appeared promising. These results indicate that clinical and environmental isolates of actinomycetes could be an interesting source of antifungal bioactive substances. The production of nonpolyenic antifungal substances by these five active isolates was investigated using several criteria: antibacterial activity, ergosterol inhibition, and UV-visible spectra of active extracts. One active strain responded to all three selection criteria and produced potentially nonpolyenic antifungal metabolites. This strain was retained for further investigation, in particular, purification, structure elucidation, and mechanism of action of the active product.Key words: actinomycetes, Streptomyces, clinical isolates, antifungal, non-polyene.
9

Brilhante, Raimunda SN, Vandbergue S. Pereira, Jonathas S. Oliveira, Anderson M. Rodrigues, Zoilo P. de Camargo, Waldemiro A. Pereira-Neto, Nilberto RF Nascimento, et al. "Terpinen-4-ol inhibits the growth of Sporothrix schenckii complex and exhibits synergism with antifungal agents." Future Microbiology 14, no. 14 (September 2019): 1221–33. http://dx.doi.org/10.2217/fmb-2019-0146.

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Aim: This study investigated the effect of terpinen-4-ol against Sporothrix schenckii complex and its interactions with antifungals. Materials & methods: The antifungal activity of terpinen-4-ol was evaluated by broth microdilution. The potential effect on cellular ergosterol concentration was evaluated by spectrophotometry. The antibiofilm activity was evaluated by violet crystal staining and XTT reduction assay. The potential pharmacological interactions with antifungals were evaluated by the checkerboard assay. Results: terpinen-4-ol (T-OH) showed minimal inhibitory concentrations ranging from 4 to 32 mg/l decreasing cellular ergosterol content and presented a SMIC ranging from 64 to 1024 mg/l for Sporothrix spp. The combinations of T-OH with itraconazole or terbinafine were synergistic. Conclusion: T-OH has antifungal activity against Sporothrix spp. and acts synergistically with standard antifungals.
10

Grayton, Quincy E., Ivie L. Conlon, Christopher A. Broberg, and Mark H. Schoenfisch. "Impact of Nitric Oxide-Release Kinetics on Antifungal Activity." Journal of Fungi 10, no. 5 (April 24, 2024): 308. http://dx.doi.org/10.3390/jof10050308.

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Pathogenic fungi are an increasing health threat due to the rise in drug resistance. The limited number of antifungals currently available and growing incidence of multi-drug-resistant fungi has caused rising healthcare costs and a decreased quality of life for patients with fungal infections. Nitric oxide (NO) has previously been shown to act as an antimicrobial agent, albeit with a limited understanding of the effects of the NO-release kinetics against pathogenic fungi. Herein, the antifungal effects of four nitric oxide-releasing small molecules were studied against the pathogenic fungi Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus, to demonstrate the broad-spectrum antifungal activity of NO. A bolus dose of NO was found to eradicate fungi after 24 h, where nitric oxide donors with shorter half-lives achieved antifungal activity at lower concentrations and thus had wider selectivity indexes. Each NO donor was found to cause a severe surface destruction of fungi, and all NO donors exhibited compatibility with currently prescribed antifungals against several different fungi species.
11

Begum, Jubeda, and P. Das. "Antifungal resistance in dermatophytosis: A global health concern." Letters In Animal Biology 2, no. 1 (May 8, 2022): 41–45. http://dx.doi.org/10.62310/liab.v2i1.76.

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Dermatophytosis is a common dermatological problem in animals as well as humans which is associated with interference in immune function. Unlike the antibacterial resistance which is frequently reported, antifungal resistance is less commonly reported, but there are reports of emerging antifungal resistance in humans and animals. The problem of antifungal resistance can be more severe in comparison to any other drug resistance due to the limited number of antifungals available for therapeutic purpose. A number of mechanisms have been put forward to explain the phenomenon of antifungal drug resistance, such as, drug efflux by fungal cells, drug detoxification by fungal cells, resistance imposed by structural elements of the fungal cell, target gene mutations, etc. Currently, only three types of antifungal drugs are available – Azoles, Polyenes, and allylamines; therefore it is mandatory to use the antifungals rationally to contain the problem of rising antifungal resistance. To counter the problem of antifungal resistance indiscriminate over the counter use of antifungal drugs in the treatment of dermatophytosis need to be strongly discouraged. Furthermore, at the research level, whole genome sequencing of dermatophytes from around the world will aid in a better understanding of fungal pathophysiology and associated drug resistance, potentially leading to new approaches to overcome antifungal resistance. And, lastly the use of combination therapy offers an advantage of synergistic action of different antifungals with enhanced spectrum activity which could play instrumental role in reducing the antifungal resistance.
12

Tscherner and Kuchler. "A Histone Acetyltransferase Inhibitor with Antifungal Activity against CTG clade Candida Species." Microorganisms 7, no. 7 (July 15, 2019): 201. http://dx.doi.org/10.3390/microorganisms7070201.

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Candida species represent one of the most frequent causes of hospital-acquired infections in immunocompromised patient cohorts. Due to a very limited set of antifungals available and an increasing prevalence of drug resistance, the discovery of novel antifungal targets is essential. Targeting chromatin modifiers as potential antifungal targets has gained attention recently, mainly due to their role in regulating virulence in Candida species. Here, we describe a novel activity for the histone acetyltransferase inhibitor Cyclopentylidene-[4-(4-chlorophenyl)thiazol-2-yl)hydrazone (CPTH2) as a specific inhibitor of CTG clade Candida species. Furthermore, we show that CPTH2 has fungicidal activity and protects macrophages from Candida-mediated death. Thus, this work could provide a starting point for the development of novel antifungals specific to CTG clade Candida species.
13

Powers, Chelsea N., Prabodh Satyal, John A. Mayo, Hana McFeeters, and Robert L. McFeeters. "Bigger Data Approach to Analysis of Essential Oils and Their Antifungal Activity against Aspergillus niger, Candida albicans, and Cryptococcus neoformans." Molecules 24, no. 16 (August 7, 2019): 2868. http://dx.doi.org/10.3390/molecules24162868.

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With increasing drug resistance and the poor state of current antifungals, the need for new antifungals is urgent and growing. Therefore, we tested a variety of essential oils for antifungal activity. We report the minimum inhibitory concentrations (MIC) values for a common set of 82 essential oils against Aspergillus niger, Candida albicans, and Cryptococcus neoformans. Generally, narrow-spectrum activity was found. However, C. neoformans was much more susceptible to inhibition by essential oils with over one-third of those tested having MIC values below 160 ppm. GC-MS analysis showed the essential oils to be chemically diverse, yet, the potentially active major constituents typically fell into a few general categories (i.e., terpenes, terpenoids, terpenols). While essential oils remain a rich source of potential antifungals, focus should shift to prioritizing activity from novel compounds outside the commonalities reported here, instead of simply identifying antifungal activity. Further, capitalizing on bigger data approaches can provide significant returns in expediting the identification of active components.
14

Cordisco, Estefanía, Maximiliano Sortino, and Laura Svetaz. "Antifungal Activity of Traditional Medicinal Plants from Argentina: Effect of their Combination with Antifungal Drugs." Current Traditional Medicine 5, no. 1 (June 3, 2019): 75–95. http://dx.doi.org/10.2174/2215083804666181002111456.

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Background and Objective: The incidence of fungal infections has experienced a marked increase in the last two decades being limited to a few drugs with serious drawbacks. Combination therapy has emerged as an approach to improve the efficacy of currently used antifungal therapy that also may delay the evolution of resistance. Method: The objectives of this work are to present a bibliographic search on the plants used in traditional medicine in Argentina for ailments related to fungal infections and to investigate the antifungal activity of currently used antifungal drugs in combination with natural extracts. Results: Results of the bibliographic investigation showed that 153 species belonging to 56 families and 120 genera from Argentina are applied to treat signs and symptoms considered to maintain ethnopharmacological uses related to fungal infections, mainly for skin and mucosal conditions. Conclusion: Regarding the evaluation of the antifungal activity of combinations between extracts and antifungal drugs, we observed that extracts from plants species belonging to a genera traditionally used for ailments related to fungal infections have more chances of enhancing the activity of amphotericin B, fluconazole and itraconazole. In addition, we observed that there is a greater chance of finding an enhancement in the activity of the commercial antifungals when the combination is performed with extracts that have shown activity in solitary. Nevertheless, inactive extracts that would have been discarded according to the classic strategy displayed activity in combination and they continue being potential candidates in the search for new antifungals.
15

Gintjee, Thomas J., Monica A. Donnelley, and George R. Thompson. "Aspiring Antifungals: Review of Current Antifungal Pipeline Developments." Journal of Fungi 6, no. 1 (February 25, 2020): 28. http://dx.doi.org/10.3390/jof6010028.

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Invasive fungal infections are associated with significant morbidity and mortality, and their management is restricted to a variety of agents from five established classes of antifungal medication. In practice, existing antifungal agents are often constrained by dose-limiting toxicities, drug interactions, and the routes of administration. An increasing prevalence of invasive fungal infections along with rising rates of resistance and the practical limitations of existing agents has created a demand for the development of new antifungals, particularly those with novel mechanisms of action. This article reviews antifungal agents currently in various stages of clinical development. New additions to existing antifungal classes will be discussed, including SUBA-itraconazole, a highly bioavailable azole, and amphotericin B cochleate, an oral amphotericin formulation, as well as rezafungin, a long-acting echinocandin capable of once-weekly administration. Additionally, novel first-in-class agents such as ibrexafungerp, an oral glucan synthase inhibitor with activity against various resistant fungal isolates, and olorofim, a pyrimidine synthesis inhibitor with a broad spectrum of activity and oral formulation, will be reviewed. Various other innovative antifungal agents and classes, including MGCD290, tetrazoles, and fosmanogepix, will also be examined.
16

Bossche, H. Vanden, P. Marichal, J. Gorrens, M. C. Coene, G. Willemsens, D. Bellens, I. Roels, H. Moereels, and P. A. J. Janssen. "Biochemical Approaches to Selective Antifungal Activity. Focus on Azole Antifungals." Mycoses 32 (November 1989): 35–52. http://dx.doi.org/10.1111/j.1439-0507.1989.tb02293.x.

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17

TSURUOKA, Akihiko, Yumiko KAKU, Hiroyuki KAKINUMA, Itaru TSUKADA, Manabu YANAGISAWA, and Toshihiko NAITO. "Synthesis and Antifungal Activity of Novel Thiazole-Containing Triazole Antifungals." CHEMICAL & PHARMACEUTICAL BULLETIN 45, no. 7 (1997): 1169–76. http://dx.doi.org/10.1248/cpb.45.1169.

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18

Horn, Connor, and Govindsamy Vediyappan. "Anticapsular and Antifungal Activity of α-Cyperone." Antibiotics 10, no. 1 (January 6, 2021): 51. http://dx.doi.org/10.3390/antibiotics10010051.

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Fungal infections affect 300 million people and cause 1.5 million deaths globally per year. With the number of immunosuppressed patients increasing steadily, there is an increasing number of patients infected with opportunistic fungal infections such as infections caused by the species of Candida and Cryptococcus. In fact, the drug-resistant Can. krusei and the emerging pan-antifungal resistant Can. auris pose a serious threat to human health as the existing limited antifungals are futile. To further complicate therapy, fungi produce capsules and spores that are resistant to most antifungal drugs/host defenses. Novel antifungal drugs are urgently needed to fill unmet medical needs. From screening a collection of medicinal plant sources for antifungal activity, we have identified an active fraction from the rhizome of Cyperus rotundus, the nut grass plant. The fraction contained α-Cyperone, an essential oil that showed fungicidal activity against different species of Candida. Interestingly, the minimal inhibitory concentration of α-Cyperone was reduced 8-fold when combined with a clinical antifungal drug, fluconazole, indicating its antifungal synergistic potential and could be useful for combination therapy. Furthermore, α-Cyperone affected the synthesis of the capsule in Cryp. neoformans, a causative agent of fungal meningitis in humans. Further work on mechanistic understanding of α-Cyperone against fungal virulence could help develop a novel antifungal agent for drug-resistant fungal pathogens.
19

Bisso, Borel Ndezo, Prudence Ngalula Kayoka-Kabongo, Roland Tchuenteu Tchuenguem, and Jean Paul Dzoyem. "Phytochemical Analysis and Antifungal Potentiating Activity of Extracts from Loquat (Eriobotrya japonica) against Cryptococcus neoformans Clinical Isolates." Advances in Pharmacological and Pharmaceutical Sciences 2022 (April 14, 2022): 1–6. http://dx.doi.org/10.1155/2022/6626834.

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Eriobotrya japonica (loquat) has been used in African traditional medicine with numerous beneficial health effects. The extracts from loquat contain several bioactive compounds with a plethora of pharmacological properties. However, a scientific study on the activity against the aetiological agent of cryptococcosis has not yet been reported. Therefore, this study aimed to investigate the antifungal potential of various extracts from Eriobotrya japonica against clinical isolates of Cryptococcus neoformans. Quantitative and qualitative phytochemical analyses of extracts were made by following standard procedures. The broth microdilution method and the checkerboard methods were used to determine the antifungal activity and the combination of extracts with antifungals drugs. The methanol extract of seeds and the hexane extract of leaves exhibited the best significant antifungal activity with MIC values of 32 µg/mL. Furthermore, the combination of both extracts with nystatin and clotrimazole showed synergistic interactions with a 32-fold reduction in the MIC values of nystatin. Our findings indicate that Eriobotrya japonica extracts are a potential source of new antifungals that could be developed for use in the treatment of cryptococcosis. The anticryptococcal and antifungal activities potentiating activity of the studied extracts indicate their potential in the management of cryptococcosis. Further study should be considered to identify the bioactive principles against Cryptococcus neoformans.
20

Ganan, Monica, Silje B. Lorentzen, Peter Gaustad, and Morten Sørlie. "Synergistic Antifungal Activity of Chito-Oligosaccharides and Commercial Antifungals on Biofilms of Clinical Candida Isolates." Journal of Fungi 7, no. 9 (September 1, 2021): 718. http://dx.doi.org/10.3390/jof7090718.

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The development of yeast biofilms is a major problem due to their increased antifungal resistance, which leads to persistent infections with severe clinical implications. The high antifungal activity of well-characterized chitosan polymers makes them potential alternatives for treating yeast biofilms. The activity of a chito-oligosaccharide with a depolymerization degree (DPn) of 32 (C32) and a fraction of acetylation (FA) of 0.15 on Candida sp. biofilms was studied. The results showed a concentration-dependent reduction in the number of viable cells present in C. albicans, C. glabrata, and C. guillermondii preformed biofilms in the presence of C32, especially on intermediate and mature biofilms. A significant decrease in the metabolic activity of yeast biofilms treated with C32 was also observed. The antifungals fluconazole (Flu) and miconazole (Mcz) decreased the number of viable cells in preformed early biofilms, but not in the intermediate or mature biofilms. Contrary to Flu or Mcz, C32 also reduced the formation of new biofilms. Interestingly, a synergistic effect on yeast biofilm was observed when C32 and Flu/Mcz were used in combination. C32 has the potential to become an alternative therapeutic agent against Candida biofilms alone or in combination with antifungal drugs and this will reduce the use of antifungals and decrease antifungal resistance.
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Tabata, Yuji, Naomi Takei-Masuda, Natsuki Kubota, Sho Takahata, Makoto Ohyama, Kaori Kaneda, Maiko Iida, and Kazunori Maebashi. "Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis." Antimicrobial Agents and Chemotherapy 60, no. 2 (December 7, 2015): 1035–39. http://dx.doi.org/10.1128/aac.01739-15.

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ABSTRACTFungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate thein vitroantifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity againstTrichophyton rubrumandTrichophyton mentagrophytes(the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50and MIC90of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition ofTrichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation.
22

Kalsum, Ummu, and Ayu Ayu. "Uji Aktivitas Ekstrak Etanol Umbi Wortel (Daucus carota L.) Sebagai Antifungi Terhadap Pertumbuhan Candida albicans." WARTA FARMASI 8, no. 2 (October 10, 2019): 71–80. http://dx.doi.org/10.46356/wfarmasi.v8i2.117.

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ABSTRAK Telah dilakukan penelitian Uji Aktivitas Ekstrak Etanol Umbi Wortel (Daucus carota L.) Sebagai Antifungi Terhadap Pertumbuhan Candida albicans. Penelitian ini bertujuan untuk mengetahui aktivitas ekstrak etanol umbi wortel sebagai antifungi terhadap pertumbuhan Candida albicans dengan menggunakan variasi konsentrasi yang berbeda yaitu 1% b/v, 3% b/v dan 5% b/v. Ekstrak etanol umbi wortel diperoleh dengan cara maserasi menggunakan pelarut etanol 70%. Pengujian aktivitas antifungi menggunakan metode difusi agar dengan cara sumuran untuk mengetahui aktivitas antifungi dengan mengamati daerah hambatan. Hasil penelitian ini menunjukkan bahwa konsentrasi ekstrak 1% b/v, 3% b/v dan 5% b/v dapat memberikan aktivitas yang menghambat pertumbuhan jamur uji. Terdapat penambahan diameter zona hambat pada setiap kenaikan konsentrasi yaitu 1% b/v (15,7 mm), 3% b/v (18,9 mm), dan 5% b/v (19,8 mm) terhadap jamur Candida albicans. Semua variasi konsentrasi ekstrak memiliki aktivitas antifungi yang kuat dalam menghambat pertumbuhan Candida albicans. Kata kunci: Ekstrak, Daucus carota L., Antifungi, Candida albicans ABSTRACT It has conducted a study of activity test of carrot tuber ethanol extract (Daucus carota L.) as antifungal toward the growth of candida albicans. This the study aims at knowing the activity of carrot tuber ethanol extract (Daucus carota L.) as antifungal toward the growth of candida albicans by using different variance concentration they are 1% b/v, 3% b/v and 5% b/v. Carrot tuber ethanol the extract was obtained by maceration by using 70% of ethanol dissolver. Activity test of antifungal by using agar diffusion method with a well method to find out the the activity of antifungal by observing the obstruction zone. The result of this research shows that concentration extract 1% b/v, 3% b/v and 5% b/v can give activity which impedes the growth of fungal test. There is increasing of obstruction zone diameter in every increment of of the concentration they are 1% b/v (15,7 mm), 3% b/v (18,9 mm) and 5% b/v (19,8mm) toward Candida albicans fungi. All extract concentration variation has a strong antifungal activity in impeding the growth of Candida albicans.
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Andrade-Ochoa, Sergio, Daniela Sánchez-Aldana, Luz María Rodríguez-Valdez, and Guadalupe Virginia Nevárez-Moorillón. "Evaluación in vitro y QSAR (Quantitative and Structure-Activity Relationship) de la actividad antifúngica de terpenoides obtenidos de aceites esenciales frente a Alternaria alternata y Fusarium oxysporum." Biomédica 43, Sp. 1 (August 31, 2023): 156–69. http://dx.doi.org/10.7705/biomedica.6883.

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Introduction. Fungal genera Alternaria and Fusarium include human and plant pathogenic species. Several antifungals have been used for their control, but excessive use has contributed to resistance development in pathogens. An alternative to searching for and developing new antifungal agents is using essential oils and their main components, which have biological activities of interest in medicine and food production.Objective. To evaluate in vitro and in silico the antifungal activities of terpenoids against Alternaria alternata and Fusarium oxysporum.Materials and methods. The minimum inhibitory concentration and minimum fungicidal concentration values of 27 constituents of essential oils used against Alternaria alternata and Fusarium oxysporum were evaluated in vitro. In addition, using genetic algorithms, quantitative models of the structure-activity relationship were used to identify the structural and physicochemical properties related to antifungal activity.Results. The evaluated compounds proved to be effective antifungals. Thymol was the most active with a minimum inhibitory concentration of 91.6 ± 28.8 μg/ml for A. alternata and F. oxysporum. Quantitative structure-activity relationship models revealed the octanolwater cleavage ratio as the molecular property, and the phenols as the main functional group contributing to antifungal activity.Conclusion. Terpenoids exhibit relevant antifungal activities that should be incorporated into the study of medicinal chemistry. Inclusion of in silico assays in the in vitro evaluation is a valuable tool in the search for and rational design of terpene derivatives as new potential antifungal agents.
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Kasamba, I. E. "Triple-Action Antifungal Topicals, Microbiologist's Alarm." Asian Journal of Biology 19, no. 1 (August 4, 2023): 37–44. http://dx.doi.org/10.9734/ajob/2023/v19i1357.

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Today, we are witnessing the development and marketing of triple action antifungals for the treatment of superficial mycoses. It is a mixture of antifungals, antibiotics and anti-inflammatory. The problem of this research was to verify the effects of this mixture as to its effectiveness on superficial mycoses. Thus, we set ourselves the following objectives: to identify the antifungals in the pharmacies of the cities of Likasi, Lubumbashi and Kolwezi, to determine their composition and to discuss this composition with the existing literature. Through a cross-sectional study, we identified thirty-four different antifungals in 588 pharmacies, of which 16 or 47.05% are triple action and made up of Azoles as antifungal, the antibiotic gentamicin, and corticosteroids as anti-inflammatory, alongside polyene, Echinocandins and flucytosine. It is the combination of antifungals with conventional non-antifungal agents reoriented for their action on the growth of fungi. They consist of antibacterial drugs and steroidal anti-inflammatories. This reorientation was supposed to have excellent antifungal activity and could prevent resistance. However, the presence of the antibiotic will reduce the composition of the colonizing microbiota and promote fungal growth and enhance fungal pathogenicity indirectly and the corticosteroid component may interfere with the therapeutic actions of the antifungal agent and may accelerate fungal growth, due to a decrease in the host's local immunological reaction, so that the underlying infection may persist, and the dermatophytes may even acquire the ability to invade the deeper tissues. So, in support, it would be interesting to favor antifungals without combinations than those combining antibiotics and anti-inflammatory which has an extremely high rate of recurrence.
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Roa-Linares, Vicky C., Ana C. Mesa-Arango, Ramón J. Zaragozá, and Miguel A. González-Cardenete. "Antifungal Activity of Amphiphilic Perylene Bisimides." Molecules 27, no. 20 (October 14, 2022): 6890. http://dx.doi.org/10.3390/molecules27206890.

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Perylene-based compounds, either naturally occurring or synthetic, have shown interesting biological activities. In this study, we report on the broad-spectrum antifungal properties of two lead amphiphilic perylene bisimides, compounds 4 and 5, which were synthesized from perylene-3,4,9,10-tetracarboxylic dianhydride by condensation with spermine and an ammonium salt formation. The antifungal activity was evaluated using a collection of fungal strains and clinical isolates from patients with onychomycosis or sporotrichosis. Both molecules displayed an interesting antifungal profile with MIC values in the range of 2–25 μM, being as active as several reference drugs, even more potent in some particular strains. The ammonium trifluoroacetate salt 5 showed the highest activity with a MIC value of 2.1 μM for all tested Candida spp., two Cryptococcus spp., two Fusarium spp., and one Neoscytalidium spp. strain. Therefore, these amphiphilic molecules with the perylene moiety and cationic ammonium side chains represent important structural features for the development of novel antifungals.
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Shalini, Kumari, Nitin Kumar, Sushma Drabu, and Pramod Kumar Sharma. "Advances in synthetic approach to and antifungal activity of triazoles." Beilstein Journal of Organic Chemistry 7 (May 25, 2011): 668–77. http://dx.doi.org/10.3762/bjoc.7.79.

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Several five membered ring systems, e.g., triazole, oxadiazole dithiazole and thiadiazole with three heteroatoms at symmetrical or asymmetrical positions have been studied because of their interesting pharmacological properties. In this article our emphasis is on synthetic development and pharmacological activity of the triazole moiety which exhibit a broad spectrum of pharmacological activity such as antifungal, antibacterial, anti-inflammatory and anticancer etc. Triazoles have increased our ability to treat many fungal infections, for example, candidiasis, cryptococcal meningitis, aspergillosis etc. However, mortality due to these infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although we are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases, the options for treatment will have greatly expanded.
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Pech-Puch, Dawrin, Diana Grilo, Susana Eunice Calva-Pérez, Andreia Pedras, Harold Villegas-Hernández, Sergio Guillén-Hernández, Raúl Díaz-Gamboa, et al. "Antifungal Potential of Marine Organisms of the Yucatan Peninsula (Mexico) against Medically Important Candida spp." Molecules 28, no. 2 (January 6, 2023): 606. http://dx.doi.org/10.3390/molecules28020606.

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Invasive fungal infections represent a global health threat. They are associated with high mortality and morbidity rates, partly due to the ineffectiveness of the available antifungal agents. The rampant increase in infections recalcitrant to the current antifungals has worsened this scenario and made the discovery of new and more effective antifungals a pressing health issue. In this study, 65 extracts from marine organisms of the Yucatan Peninsula, Mexico, were screened for antifungal activity against Candida albicans and Candida glabrata, two of the most prevalent fungal species that cause nosocomial invasive fungal infections worldwide. A total of 51 sponges, 13 ascidians and 1 gorgonian were collected from the coral reef and mangrove forest in the Yucatan Peninsula (Mexico) and extracted with organic solvents. Nine crude extracts showed potent antifungal activity, of which four extracts from the sponge species Aiolochroia crassa, Amphimedon compressa, Monanchora arbuscula and Agelas citrina had promising activity against Candida spp. Bioassay-guided fractionation of the M. arbuscula extract revealed the remarkable fungicidal activity of some fractions. Analysis of the chemical composition of one of the most active fractions by UHPLC-HRMS and NMR indicated the presence of mirabilin B and penaresidin B, and their contribution to the observed antifungal activity is discussed. Overall, this work highlights marine organisms of the Yucatan Peninsula as important reservoirs of natural products with promising fungicidal activity, which may greatly advance the treatment of invasive fungal infections, especially those afflicting immunosuppressed patients.
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Sharafutdinov, Irshad S., Georgii D. Ozhegov, Alina E. Sabirova, Valentina V. Novikova, Svetlana A. Lisovskaya, Alsu M. Khabibrakhmanova, Almira R. Kurbangalieva, Mikhail I. Bogachev, and Airat R. Kayumov. "Increasing Susceptibility of Drug-Resistant Candida albicans to Fluconazole and Terbinafine by 2(5H)-Furanone Derivative." Molecules 25, no. 3 (February 2, 2020): 642. http://dx.doi.org/10.3390/molecules25030642.

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The frequency of mycoses caused by drug-resistant fungal pathogen Candida albicans has increased drastically over the last two decades. The spread of drug-resistant strains, along with the limitations of currently available antifungals, complicates the management of fungal infections, thereby representing great challenges for clinical healthcare. Among various antimicrobial pharmacophores, 2(5H)-furanone derivatives have demonstrated antimicrobial, antifungal, and antibiofilm activities. In this study, we report the antifungal activity of the 2(5H)-furanone derivative F105, consisting of three pharmacophores, namely chlorinated 2(5H)-furanone, sulfonyl group, and l-menthol moiety. Although exhibiting moderate antifungal activity alone with the minimum inhibitory concentration (MIC) values of 32–256 μg/mL, F105 potentiates the activity of fluconazole and terbinafine with fractional inhibitory concentration index (FICI) values of 0.27–0.50. Thus, 16 μg/mL of F105 reduced the MICs of these antifungals against fluconazole-resistant C. albicans isolates four-fold, achieving similar values as for the intermediately susceptible phenotype. Confocal laser scanning microscopy revealed that the fluorescent 2(5H)-furanone derivative F145 was also able to penetrate through biofilms formed by C. albicans. Indeed, in the presence of F105, even sub-MIC concentrations of both fluconazole and terbinafine led to significant reduction of C. albicans CFUs in the mature biofilm. Thus, F105 appears to be a promising candidate for the development of novel antifungal agents as well as enhancers of current antifungal agents, particularly for the treatment of drug-resistant C. albicans infections.
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Krauß, Jürgen, Christoph Müller, Monika Klimt, Leandro Jorquera Valero, José Francisco Martínez, Martin Müller, Karin Bartel, Ulrike Binder, and Franz Bracher. "Synthesis, Biological Evaluation, and Structure–Activity Relationships of 4-Aminopiperidines as Novel Antifungal Agents Targeting Ergosterol Biosynthesis." Molecules 26, no. 23 (November 28, 2021): 7208. http://dx.doi.org/10.3390/molecules26237208.

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The aliphatic heterocycles piperidine and morpholine are core structures of well-known antifungals such as fenpropidin and fenpropimorph, commonly used as agrofungicides, and the related morpholine amorolfine is approved for the treatment of dermal mycoses in humans. Inspired by these lead structures, we describe here the synthesis and biological evaluation of 4-aminopiperidines as a novel chemotype of antifungals with remarkable antifungal activity. A library of more than 30 4-aminopiperidines was synthesized, starting from N-substituted 4-piperidone derivatives by reductive amination with appropriate amines using sodium triacetoxyborohydride. Antifungal activity was determined on the model strain Yarrowia lipolytica, and some compounds showed interesting growth-inhibiting activity. These compounds were tested on 20 clinically relevant fungal isolates (Aspergillus spp., Candida spp., Mucormycetes) by standardized microbroth dilution assays. Two of the six compounds, 1-benzyl-N-dodecylpiperidin-4-amine and N-dodecyl-1-phenethylpiperidin-4-amine, were identified as promising candidates for further development based on their in vitro antifungal activity against Candida spp. and Aspergillus spp. Antifungal activity was determined for 18 Aspergillus spp. and 19 Candida spp., and their impact on ergosterol and cholesterol biosynthesis was determined. Toxicity was determined on HL-60, HUVEC, and MCF10A cells, and in the alternative in vivo model Galleria mellonella. Analysis of sterol patterns after incubation gave valuable insights into the putative molecular mechanism of action, indicating inhibition of the enzymes sterol C14-reductase and sterol C8-isomerase in fungal ergosterol biosynthesis.
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Rachmani, Eka Prasasti Nur, Hanif Nasiatul Baroroh, Rehana Rehana, and Novia Ayu Rahmawati. "Antifungal activity of Calophyllum soulattri leaf extract on fungal isolate of coconut neera." Acta Pharmaciae Indonesia : Acta Pharm Indo 10, no. 2 (August 1, 2022): 5929. http://dx.doi.org/10.20884/1.api.2022.10.2.5929.

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Background: Coconut neera is susceptible to fungus contamination. Some plants, such as Calophyllum soulattri, can function as natural preservatives with antifungal properties. Objective: This study aimed to evaluate the antifungal activity of C. soulattri leaf extract as measured by minimum inhibitory concentration (MIC) and minimum killing concentration (MKC). Methods: A dilution method was used to isolate the fungus that contaminated coconut neera. MIC and MKC antifungal activity were then evaluated using the liquid dilution method. Results: The results indicated that the contaminant fungi found in coconut neera belonged to the genus Penicillium. The MIC was 12.5%, while the MKC was 18.75%. Conclusion: C. soulattri leaf extract has the potential to be developed as an antifungals for food preservation.
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Lahlou, Y., B. El Amraoui, M. El Wahidi, S. Moujabbir, A. Aboukhalaf, and T. Bamhaoud. "Evaluation of the anti-Candida albicans and anti-Cryptococcus neoformans activity of the essential oils of three Moroccan medicinal plants." IOP Conference Series: Earth and Environmental Science 1090, no. 1 (October 1, 2022): 012026. http://dx.doi.org/10.1088/1755-1315/1090/1/012026.

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Abstract The results reported in this study provide new information about the antifungal activity of these medicinal plants and suggest their uses in the high incidence of fungal infections caused by Candida albicans and Cryptococcus neoformans is due to several factors as resistance to antifungals, a fungistatic than the fungicidal effect of these drugs and the side effects of synthetic antifungals. Then, the search for new sources of molecules effective against pathogenic fungi is a major objective. In this context, the screening of antifungal activity of essential oils of three medicinal plants from Morocco (Lavandula angustifolia, Salvia officinalis, and Rosmarinus officinalis) has been carried out against C. albicans and C. neoformans, using Disk-diffusion assay and micro-dilution method. The essential oils are obtained by Hydrodistillation, the characterization of the most active essential oil was carried out by Fourier transform infrared spectroscopy (FTIR). The results show that L. angustifolia essential oil is the only oil that showed strong fungicidal activity against C. neoformans and against C. albicans. The FTIR analysis of this oil showed the existence of several antifungal compounds, mainly linalool, linalyl acetate, terpinene-4-ol, carvacrol, and citral. S. officinalis essential oil has a fungicidal effect against C. neoformans, but a fungistatic effect against C. albicans. This activity is due to the presence of camphor, 1,8-cineole, and limonene. R. officinalis essential oil showed a fungistatic effect depending on its main chemical components, including eucalyptol, limonene, cymene, α-pinene, and camphor. The results reported in this study provide new information about the antifungal activity of these medicinal plants and suggests their uses in the extraction of active principle for the synthesis of new antifungal drugs.
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Cely-Veloza, Willy-Fernando, Diego Quiroga, and Ericsson Coy-Barrera. "Diethyl 2-((aryl(alkyl)amino)methylene)malonates: Unreported Mycelial Growth Inhibitors against Fusarium oxysporum." Molbank 2023, no. 2 (April 23, 2023): M1630. http://dx.doi.org/10.3390/m1630.

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This paper presents the discovery and development of antifungal agents against Fusarium oxysporum (Fox), a devastating plant pathogen. Diethyl 2-((arylamino)methylene)malonates (DAMMs) were formed as side-products during the synthesis of polysubstituted-2-pyridones through a three-component domino reaction and seemed to have antifungal activity against Fox. DAMMs are typically employed as intermediates or precursors to produce further bioactive compounds, but they have never been examined as antifungals. To confirm this latter characteristic, we employed a single-step procedure (i.e., the first step of the Gould-Jacobs reaction) to prepare five DAMMs (74–96% yields) which were subsequently evaluated against Fox in terms of their abilities to inhibit mycelial growth. The antifungal outcome was promising (0.013 µM < IC50 < 35 µM), involving fungistatic or fungicide effects. This small group of active compounds showed differences in antifungal activity, constituting the basis of further studies to expand the DAMM chemical space and look for improved antifungal activity.
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A., Umadevi, Champa Kumari, P. Ajith Kumar, Hameemath Shamana Nasmin Am, Divya K., and Hisana P. V. "DEVELOPMENT AND EVALUATION OF POLYHERBAL GEL FOR ANTIFUNGAL ACTIVITY." International Journal of Current Pharmaceutical Research 10, no. 5 (September 15, 2018): 40. http://dx.doi.org/10.22159/ijcpr.2018v10i5.29694.

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Objective: Piper betal and Piper nigrumare traditional medicinal plants that have antifungal activity against Candida albicans, a combination of these two plants have not been known for its activity against this fungus. The purpose of this research was to formulate topical gel, a combination of P. betal and P. nigram which has antifungal activity against Candida albicans.Methods: The antifungal activity test of P. betal and P. nigrum using agar well diffusion method was carried out. Thereafter, a topical gel formulation was prepared using Sodium carboxymethyl cellulose as a gelling agent of concentration 1; 1.5 and 2%. Test parameters for topical gel includes organoleptic, pH, extrudability, spreadability, diffusion, and stability test.Result: The results of this study showed that P. betel and P. nigrum extracts had antifungal activity. Antifungal activity combination of P. betel and P. nigrum leaf extract is synergistic. For the formulation materials, the concentration chosen is 1: 1 (P. betel: P. nigrum) because in that combination the value of the resistor area is still categorized well. The stability test results stated that all the formulas were stable even after 30 d of stability studies.Conclusion: This is the first report on the scientific evaluation of betel and pepper leaf extracts combination as a gel for antifungal activity. Thus our study reveals both leaf extracts to be good antifungals; their methanolic hydro extracts may be formulated as hydrogels with satisfactory physicochemical parameters.
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Nivoix, Yasmine, Marie-Pierre Ledoux, and Raoul Herbrecht. "Antifungal Therapy: New and Evolving Therapies." Seminars in Respiratory and Critical Care Medicine 41, no. 01 (January 30, 2020): 158–74. http://dx.doi.org/10.1055/s-0039-3400291.

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AbstractInvasive fungal diseases primarily occur in immunocompromised patients. Immunosuppression has become more prevalent due to novel treatments, and this has led to a rise in the incidence of invasive fungal diseases. The antifungal armamentarium has long been insufficient and has taken quite some time to become diverse. Antifungal spectrum, tolerability, and toxicity are critical issues. Amphotericin B and its lipid formulations still have the widest spectrum, but, in spite of the better tolerance of the lipid formulations, toxicity remains a drawback, mostly with regard to renal function. Azoles constitute a heterogeneous antifungal class, in which newer molecules have an improved spectrum of activity. The main concern for the clinician when using azoles relates to the management of their many potential drug–drug interactions in an often fragile patient population. Echinocandins are better tolerated but possess a narrower antifungal spectrum and lack an oral route of administration. Still, their fungicidal activity makes them a weapon of first choice against Candida species. For certain uncommon fungal infections, antifungals such as flucytosine and terbinafine can also be useful. This article will give an overview of the mechanisms of action of currently used antifungals, as well as their spectrum of activity, clinically relevant pharmacological features, drug–drug interactions, and frequent side effects, all of which should drive the clinician's choice of agent when managing invasive fungal infections.
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Keller, Petra, Christoph Müller, Isabel Engelhardt, Ekkehard Hiller, Karin Lemuth, Holger Eickhoff, Karl-Heinz Wiesmüller, Anke Burger-Kentischer, Franz Bracher, and Steffen Rupp. "An Antifungal Benzimidazole Derivative Inhibits Ergosterol Biosynthesis and Reveals Novel Sterols." Antimicrobial Agents and Chemotherapy 59, no. 10 (July 27, 2015): 6296–307. http://dx.doi.org/10.1128/aac.00640-15.

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ABSTRACTFungal infections are a leading cause of morbidity and death for hospitalized patients, mainly because they remain difficult to diagnose and to treat. Diseases range from widespread superficial infections such as vulvovaginal infections to life-threatening systemic candidiasis. For systemic mycoses, only a restricted arsenal of antifungal agents is available. Commonly used classes of antifungal compounds include azoles, polyenes, and echinocandins. Due to emerging resistance to standard therapies, significant side effects, and high costs for several antifungals, there is a need for new antifungals in the clinic. In order to expand the arsenal of compounds with antifungal activity, we previously screened a compound library using a cell-based screening assay. A set of novel benzimidazole derivatives, including (S)-2-(1-aminoisobutyl)-1-(3-chlorobenzyl)benzimidazole (EMC120B12), showed high antifungal activity against several species of pathogenic yeasts, includingCandida glabrataandCandida krusei(species that are highly resistant to antifungals). In this study, comparative analysis of EMC120B12 versus fluconazole and nocodazole, using transcriptional profiling and sterol analysis, strongly suggested that EMC120B12 targets Erg11p in the ergosterol biosynthesis pathway and not microtubules, like other benzimidazoles. In addition to the marker sterol 14-methylergosta-8,24(28)-dien-3β,6α-diol, indicating Erg11p inhibition, related sterols that were hitherto unknown accumulated in the cells during EMC120B12 treatment. The novel sterols have a 3β,6α-diol structure. In addition to the identification of novel sterols, this is the first time that a benzimidazole structure has been shown to result in a block of the ergosterol pathway.
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Hein, Kyaw Zaw, Hitoshi Takahashi, Toshiko Tsumori, Yukihiko Yasui, Yasuko Nanjoh, Tetsuo Toga, Zhihong Wu, et al. "Disulphide-reduced psoriasin is a human apoptosis-inducing broad-spectrum fungicide." Proceedings of the National Academy of Sciences 112, no. 42 (October 5, 2015): 13039–44. http://dx.doi.org/10.1073/pnas.1511197112.

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The unexpected resistance of psoriasis lesions to fungal infections suggests local production of an antifungal factor. We purified Trichophyton rubrum-inhibiting activity from lesional psoriasis scale extracts and identified the Cys-reduced form of S100A7/psoriasin (redS100A7) as a principal antifungal factor. redS100A7 inhibits various filamentous fungi, including the mold Aspergillus fumigatus, but not Candida albicans. Antifungal activity was inhibited by Zn2+, suggesting that redS100A7 interferes with fungal zinc homeostasis. Because S100A7-mutants lacking a single cysteine are no longer antifungals, we hypothesized that redS100A7 is acting as a Zn2+-chelator. Immunogold electron microscopy studies revealed that it penetrates fungal cells, implicating possible intracellular actions. In support with our hypothesis, the cell-penetrating Zn2+-chelator TPEN was found to function as a broad-spectrum antifungal. Ultrastructural analyses of redS100A7-treated T. rubrum revealed marked signs of apoptosis, suggesting that its mode of action is induction of programmed cell death. TUNEL, SYTOX-green analyses, and caspase-inhibition studies supported this for both T. rubrum and A. fumigatus. Whereas redS100A7 can be generated from oxidized S100A7 by action of thioredoxin or glutathione, elevated redS100A7 levels in fungal skin infection indicate induction of both S100A7 and its reducing agent in vivo. To investigate whether redS100A7 and TPEN are antifungals in vivo, we used a guinea pig tinea pedes model for fungal skin infections and a lethal mouse Aspergillus infection model for lung infection and found antifungal activity in both in vivo animal systems. Thus, selective fungal cell-penetrating Zn2+-chelators could be useful as an urgently needed novel antifungal therapeutic, which induces programmed cell death in numerous fungi.
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Chai, Shuang, Jing-Lun Zhan, Li-Mei Zhao, and Xiao-Dong Liu. "Safety of triazole antifungals: a pharmacovigilance study from 2004 to 2021 based on FAERS." Therapeutic Advances in Drug Safety 13 (January 2022): 204209862211432. http://dx.doi.org/10.1177/20420986221143266.

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Background: Triazole antifungals are widely used as broad-spectrum antifungal activity; however, there are many undetected and unreported adverse events (AEs). Methods: Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter (Q1) of 2004 to the third quarter (Q3) of 2021 were selected for disproportionality analysis to assess the connection between antifungal triazoles, and AEs and important medical events (IMEs). Results: A total of 22,566 records associated with triazole antifungals were identified, with 9584 triazole antifungal–IME pairs. The following system organ classes (SOCs) appeared as significant signals: ‘Endocrine disorders’ [reported odds ratio (ROR) = 167.94], ‘Metabolism and nutrition disorders’ (ROR = 46.30), and ‘Skin and subcutaneous tissue disorders’ (ROR = 21.37). Strong signals were observed with respiratory failure, rash, hepatic function abnormal, and hypokalemia. Uncommon security signals included a change in the QT interval, neurotoxicity, pseudoaldosteronism, and hallucinations. Conclusion: Various triazole antifungals cause AEs of different types and intensities of association. Our results are broadly consistent with prescribing information and previous studies; however, additional pharmacoepidemiological studies are required to verify AEs with modest incidence but high signal. Plain Language Summary A study on the adverse effects of triazole antifungals Introduction: The triazole antifungals we studied include fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole. Triazole antifungals are widely used as broad-spectrum antifungals; however, there are many undetected and unreported adverse events (AEs). Materials and Methods: The Food and Drug Administration Adverse Event Reporting System (FAERS) database contains AEs reported to the FDA by different countries regarding post-marketing drugs. Through the FAERS database, we retrieved a total of 22,566 AE reports related to triazole antifungals. We not only counted information about patients’ gender, age, weight, reporting country, outcome indicators, and indications but also analyzed the system organ classes (SOCs) of AEs, and the number of reported drug-related AEs and the degree of relevance. Results: We found a total of 22,566 records related to triazole antifungal agents, of which 9584 reports made important medical events (IMEs) about triazole antifungal agents, which are serious AEs. The following SOCs appear as important signals: ‘endocrine disorders’, ‘metabolic and nutritional disorders’, and ‘skin and subcutaneous tissue disorders’. Triazole antifungals produce AEs, such as respiratory failure, rash, hepatic function abnormal, and hypokalemia. They also produce uncommon AEs, including changes in the QT interval, neurotoxicity, pseudoaldosteronism, and hallucinations. Conclusion: By analyzing data from the FAERS database, we identified more AEs associated with these five triazole antifungals than were indicated in the instructions and our findings provide additional insight into triazole-related AEs to inform clinicians before and during treatment.
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Leite-Andrade, Melyna Chaves, Luiz Nascimento de Araújo Neto, Maria Daniela Silva Buonafina-Paz, Franz de Assis Graciano dos Santos, Adryelle Idalina da Silva Alves, Maria Carolina Accioly Brelaz de Castro, Edna Mori, et al. "Antifungal Effect and Inhibition of the Virulence Mechanism of D-Limonene against Candida parapsilosis." Molecules 27, no. 24 (December 14, 2022): 8884. http://dx.doi.org/10.3390/molecules27248884.

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Yeasts from the Candida parapsilosis complex are clinically relevant due to their high virulence and pathogenicity potential, such as adherence to epithelial cells and emission of filamentous structures, as well as their low susceptibility to antifungals. D-limonene, a natural compound, emerges as a promising alternative with previously described antibacterial, antiparasitic, and antifungal activity; however, its mechanisms of action and antivirulence activity against C. parapsilosis complex species have not been elucidated. Therefore, in the present study, we aimed to evaluate the antifungal and antivirulence action, as well as the mechanism of action of D-limonene against isolates from this complex. D-limonene exhibited relevant antifungal activity against C. parapsilosis complex yeasts, as well as excellent antivirulence activity by inhibiting yeast morphogenesis and adherence to the human epithelium. Furthermore, the apoptotic mechanism induced by this compound, which is not induced by oxidative stress, represents an important target for the development of new antifungal drugs.
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Heredero-Bermejo, Irene, Natalia Gómez-Casanova, Sara Quintana, Juan Soliveri, Francisco Javier de la Mata, Jorge Pérez-Serrano, Javier Sánchez-Nieves, and José Luis Copa-Patiño. "In Vitro Activity of Carbosilane Cationic Dendritic Molecules on Prevention and Treatment of Candida Albicans Biofilms." Pharmaceutics 12, no. 10 (September 25, 2020): 918. http://dx.doi.org/10.3390/pharmaceutics12100918.

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Candida spp. are one of the most common fungal pathogens. Biofilms formed by Candidaalbicans offer resistance mechanisms against most antifungal agents. Therefore, development of new molecules effective against these microorganisms, alone or in combination with antifungal drugs, is extremely necessary. In the present work, we carried out a screening process of different cationic carbosilane dendritic molecules against C. albicans. In vitro activity against biofilm formation and biofilms was tested in both Colección Española de Cultivos Tipo (CECT) 1002 and clinical C. albicans strains. Cytotoxicity was studied in human cell lines, and biofilm alterations were observed by scanning electron microscopy (SEM). Antifungal activity of the carbosilane dendritic molecules was assessed by monitoring cell viability using both established and novel cell viability assays. One out of 14 dendritic molecules tested, named BDSQ024, showed the highest activity with a minimum biofilm inhibitory concentration (MBIC) for biofilm formation and a minimum biofilm damaging concentration (MBDC) for existing biofilm of 16–32 and 16 mg/L, respectively. Synergy with amphotericin (AmB) and caspofungin (CSF) at non-cytotoxic concentrations was found. Therefore, dendritic compounds are exciting new antifungals effective at preventing Candida biofilm formation and represent a potential novel therapeutic agent for treatment of C. albicans infection in combination with existing clinical antifungals.
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Basset, Charlie, Véronique Eparvier, and Laila S. Espindola. "The Search for Antifungals from Amazonian Trees: A Bio-Inspired Screening." Natural Product Communications 10, no. 4 (April 2015): 1934578X1501000. http://dx.doi.org/10.1177/1934578x1501000417.

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The anti-fungal activity of 60 extracts from 15 tree species in the French Guiana rainforest against human and wood-rotting fungi was studied. In this way (+)-mopanol (1) was isolated from the ethyl acetate extract of Peltogyne sp. (Caesalpiniaceae) wood. This work demonstrated that (1) the natural durability of wood can indeed guide the search for antifungal agents, (2) that extracts selected in this bio-inspired process exhibit a broad spectrum of antifungal activity and (3) that the method allows for the isolation of strongly active antifungals.
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Paramastri, Prasasti Kusumaning, and Muhammad Taufiq Qurrohman. "Efektifitas Ekstrak Lidah Mertua (Sansevieria trifasciata var laurentii) Sebagai Antifungi Candida albicans." JOURNAL OF MUHAMMADIYAH MEDICAL LABORATORY TECHNOLOGIST 5, no. 2 (December 3, 2022): 149. http://dx.doi.org/10.30651/jmlt.v5i2.13478.

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Candidiasis is a disease caused by Candida albicans, this disease has a mortality rate of > 25%, mainly affecting adults, with a frequency of women 2 - 3 times more than men (Raningsih et al., 2018). A commonly used fungi drug is ketoconazole. but it has many side effects so it is necessary to find for alternatives to natural ingredients, namely the leaf of lidah mertua (Sansevieria trifasciata var laurentii) because it contains compounds saponins, flavonoids, triterpenoids, and steroids as antifungals The leaf of lidah mertua were extracted by maceration technique. The purpose of this research was to determine the effect of antifungi of ethanol extract the leaf of Lidah Mertua (Sansiviera trifasciata var Laurentii) against the fungus Candida albicans. This research was experimental using the disc diffusion method with a spread plate technique in the inhibition zone formed at concentrations of 25%, 20%, 15%, 10%, 5%, positive control and negative control. The results of the One way Anova test is known that differ significantly. From the results of this research, it can be concluded that the ethanol extract of the leaves of the leaf of lidah mertua (Sansevieria trifasciata var laurentii) has an effect on the antifungal activity of Candida albicans Keywords : Candida albicans, Leaf of Lidah Mertua, Antifungal, Ketokonazole
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Xiong, Zirui Ray, Mario Cobo, Randy M. Whittal, Abigail B. Snyder, and Randy W. Worobo. "Purification and characterization of antifungal lipopeptide produced by Bacillus velezensis isolated from raw honey." PLOS ONE 17, no. 4 (April 6, 2022): e0266470. http://dx.doi.org/10.1371/journal.pone.0266470.

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Raw honey contains a diverse microbiota originating from honeybees, plants, and soil. Some gram-positive bacteria isolated from raw honey are known for their ability to produce secondary metabolites that have the potential to be exploited as antimicrobial agents. Currently, there is a high demand for natural, broad-spectrum, and eco-friendly bio-fungicides in the food industry. Naturally occurring antifungal products from food-isolated bacteria are ideal candidates for agricultural applications. To obtain novel antifungals from natural sources, we isolated bacteria from raw clover and orange blossom honey to evaluate their antifungal-producing potential. Two Bacillus velezensis isolates showed strong antifungal activity against food-isolated fungal strains. Antifungal compound production was optimized by adjusting the growth conditions of these bacterial isolates. Extracellular proteinaceous compounds were purified via ammonium sulfate precipitation, solid phase extraction, and RP-HPLC. Antifungal activity of purified products was confirmed by deferred overlay inhibition assay. Mass spectrometry (MS) was performed to determine the molecular weight of the isolated compounds. Whole genome sequencing (WGS) was conducted to predict secondary metabolite gene clusters encoded by the two antifungal-producing strains. Using MS and WGS data, we determined that the main antifungal compound produced by these two Bacillus velezensis isolates was iturin A, a lipopeptide exhibiting broad spectrum antifungal activity.
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Rayan, Mahmoud, Ziyad Abdallah, Saleh Abu-Lafi, Mahmud Masalha, and Anwar Rayan. "Indexing Natural Products for their Antifungal Activity by Filters-based Approach: Disclosure of Discriminative Properties." Current Computer-Aided Drug Design 15, no. 3 (April 10, 2019): 235–42. http://dx.doi.org/10.2174/1573409914666181017100532.

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<P>Background: A considerable worldwide increase in the rate of invasive fungal infections and resistance toward antifungal drugs was witnessed during the past few decades. Therefore, the need for newer antifungal candidates is paramount. Nature has been the core source of therapeutics for thousands of years, and an impressive number of modern drugs including antifungals were derived from natural sources. In order to facilitate the recognition of potential candidates that can be derived from natural sources, an iterative stochastic elimination optimization technique to index natural products for their antifungal activity was utilized. Methods: A set of 240 FDA-approved antifungal drugs, which represent the active domain, and a set of 2,892 natural products, which represent the inactive domain, were used to construct predictive models and to index natural products for their antifungal bioactivity. The area under the curve for the produced predictive model was 0.89. When applying it to a database that is composed of active/inactive chemicals, we succeeded to detect 42% of the actives (antifungal drugs) in the top one percent of the screened chemicals, compared with one-percent when using a random model. Results and Conclusion: Eight natural products, which were highly scored as likely antifungal drugs, are disclosed. Searching PubMed showed only one molecule (Flindersine) out of the eight that have been tested was reported as an antifungal. The other seven phytochemicals await evaluation for their antifungal bioactivity in a wet laboratory.</P>
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Edwards, Jessica A., Megan M. Kemski, and Chad A. Rappleye. "Identification of an Aminothiazole with Antifungal Activity against Intracellular Histoplasma capsulatum." Antimicrobial Agents and Chemotherapy 57, no. 9 (July 1, 2013): 4349–59. http://dx.doi.org/10.1128/aac.00459-13.

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ABSTRACTAs eukaryotes, fungi possess relatively few molecules sufficiently unique from mammalian cell components to be used as drug targets. Consequently, most current antifungals have significant host cell toxicity. Primary fungal pathogens (e.g.,Histoplasma) are of particular concern, as few antifungals are effective in treating them. To identify additional antifungal candidates for the treatment of histoplasmosis, we developed a high-throughput platform for monitoringHistoplasmagrowth and employed it in a phenotypic screen of 3,600 commercially available compounds. Seven hit compounds that inhibitedHistoplasmayeast growth were identified. Compound 41F5 has fungistatic activity againstHistoplasmayeast at micromolar concentrations, with a 50% inhibitory concentration (IC50) of 0.87 μM, and has the greatest selectivity for yeast (at least 62-fold) relative to host cells. Structurally, 41F5 consists of an aminothiazole core with an alicyclic substituent at the 2-position and an aromatic substituent at the 5-position. 41F5 inhibitsHistoplasmagrowth in liquid culture and similarly inhibits yeast cells within macrophages, the actual host environment of this fungal pathogen during infection. Importantly, 41F5 protects infected host cells fromHistoplasma-induced macrophage death, making this aminothiazole hit compound an excellent candidate for development as an antifungal forHistoplasmainfections.
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Ustamuni, Ustamuni, Laily Nurliana, and Rustam Musta. "Aplikasi dan Tinjauan Kinetika Hasil Fraksinasi Produk Pirolisis Cangkang Biji Jambu Mete Uji sebagai Antijamur Candida albicans." IJCA (Indonesian Journal of Chemical Analysis) 2, no. 2 (September 23, 2019): 47–53. http://dx.doi.org/10.20885/ijca.vol2.iss2.art1.

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Research on application and kinetics study of fractionation pyrolysis product from cashew nut shell as antifungal of Candida albicans has been carried out. This study aims to determine the constituent compounds, antifungal activity and chemical kinetics including order and rate constants antifungal activity C. albicans from fractional distillation results of cashew nut shell pyrolysis products. Cashew nuts were hydrolyzed and purified using a fractional distillation device. The results of the antifungal activity test C. albicans from fractional distillation results of cashew nut shell pyrolysis products showed that the inhibitory power varied from each concentration variation of 12.5%, 25%, 50%, 75%, and 100%. The concentration of 100% was the highest inhibitory characterized by the formation of a clear zone of 18.23 mm which indicates that the inhibitory force is a strong category. The clear zone that has been formed was calculated in terms of its chemical kinetics including the reaction order and the activity rate constant. The reaction order of antifungals C. albicans from the results of fractional distillation of cashew nut shell pyrolysis products is 0.15 with a constant activity rate of 8.74.
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Babu, Geethavani, Balamuruganvelu Singaravelu, Sreenivasalu Reddy Vallapu, and Srikumar Ramasundaram. "IN VITRO ANTIFUNGAL ACTIVITY OF FLOWER EXTRACT OF PANDANUS ODORATISSIMUS AGAINST DERMATOPHYTIC FUNGI." Asian Journal of Pharmaceutical and Clinical Research 11, no. 9 (September 7, 2018): 325. http://dx.doi.org/10.22159/ajpcr.2018.v11i9.27082.

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Objective: The present study aimed to evaluate the antifungal activity of Pandanus odoratissimus oil against dermatophytic fungi, and it was compared against the two commonly used antifungal agent’s fluconazole and griseofulvin.Methods: A total of seven strains of dermatophytes were tested for antifungal activity using oil extracted from the flower of P. odoratissimus by using agar-well diffusion method and the zone of inhibition was compared with antifungal agent’s fluconazole and griseofulvin. Minimum inhibitory concentration (MIC) was determined using the tube-dilution method.Results and Conclusion: The zone of inhibition varied from 16.32 to 19.76 mm for fluconazole, 12.12–18.16 mm for griseofulvin, and 2.5–9.59 mm and 7.63–12.88 mm for 2.5 mg/ml and 5 mg/ml of P. odoratissimus extract, respectively. Epidermophyton floccosum and Trichophyton violaceum showed the lowest MIC value of 0.15 mg/ml. The results of our study have shown that the extract from P. odoratissimus can work significantly better against fungal diseases caused by dermatophytes. It was also found that it acts as a perfect alternative to the currently available antifungals such as fluconazole and griseofulvin.
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Li-Zhulanov, Nikolai S., Nadezhda P. Zaikova, Suat Sari, Dolunay Gülmez, Suna Sabuncuoğlu, Keriman Ozadali-Sari, Sevtap Arikan-Akdagli, et al. "Rational Design of New Monoterpene-Containing Azoles and Their Antifungal Activity." Antibiotics 12, no. 5 (April 27, 2023): 818. http://dx.doi.org/10.3390/antibiotics12050818.

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Azole antifungals, including fluconazole, have long been the first-line antifungal agents in the fight against fungal infections. The emergence of drug-resistant strains and the associated increase in mortality from systemic mycoses has prompted the development of new agents based on azoles. We reported a synthesis of novel monoterpene-containing azoles with high antifungal activity and low cytotoxicity. These hybrids demonstrated broad-spectrum activity against all tested fungal strains, with excellent minimum inhibitory concentration (MIC) values against both fluconazole-susceptible and fluconazole-resistant strains of Candida spp. Compounds 10a and 10c with cuminyl and pinenyl fragments demonstrated up to 100 times lower MICs than fluconazole against clinical isolates. The results indicated that the monoterpene-containing azoles had much lower MICs against fluconazole-resistant clinical isolates of Candida parapsilosis than their phenyl-containing counterpart. In addition, the compounds did not exhibit cytotoxicity at active concentrations in the MTT assay, indicating potential for further development as antifungal agents.
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Carrillo, A. J., and J. Guarro. "In Vitro Activities of Four Novel Triazoles againstScedosporium spp." Antimicrobial Agents and Chemotherapy 45, no. 7 (July 1, 2001): 2151–53. http://dx.doi.org/10.1128/aac.45.7.2151-2153.2001.

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ABSTRACT In order to develop new approaches to the treatment of the severe and usually fatal infections caused by Scedosporiumspp., the in vitro antifungal activities of four novel triazoles (posaconazole, ravuconazole, voriconazole, and UR-9825) and some current antifungals (amphotericin B, ketoconazole, itraconazole, and nystatin) were determined. The latter group was clearly ineffective against the two species tested. The four new antifungals showed activity against Scedosporium apiospermum, and UR-9825 and voriconazole were active against S. prolificans.
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A, Alognon, Poli S, Montant MES, Hoinsou Y, Gbati L, Gbekley EH, and Djeri B. "Antifungal activity of African medicinal plants: a review." Open Access Journal of Science 6, no. 1 (July 31, 2023): 80–84. http://dx.doi.org/10.15406/oajs.2023.06.00197.

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In Africa many plants are used as antifungals. However, journals analysing the work of antifungal activities of plants in West Africa in recent years are rare. This study is a synthesis of publications from 2006 to 2021 on plants traditionally used in the fight against antifungal diseases. A systematic search was carried out in the Pub Med and Google Scholar database using the following keywords: vaginitis; West Africa; antifungal activity; medicinal plants; plant extracts; for articles published from 2006 to 2021. These selected articles focus on ethnobotanical studies, in vitro antifungal tests and molecules isolated from these plants. A total of 46 papers were selected from 7 West African countries with 56 plants studied. Nigeria and Ivory coast did more work with 22 and 14 papers respectively and studied more plants with 23 and 17 respectively. 43% of plants show good activity in vitro on strains of Candida albicans in the laboratory with a minimum fungicide concentration and a percentage of inhibition above 50%. The most active extracts are found in Ivory coast with respectively the hexane extracts of Terminalia mantaly with a minimum fungicide concentration= 0.024 mg / mL and the hydroethanolic extract of Terminalia ivorensis with a minimum fungicide concentration of 0.097 mg / mL. It is clear that the traditional West African pharmacopoeia can make an important contribution for the management of vaginitis.
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Burduniuc, Olga, Andra-Cristina Bostanaru, Mihai Mares, Gabriela Biliuta, and Sergiu Coseri. "Synthesis, Characterization, and Antifungal Activity of Silver Nanoparticles Embedded in Pullulan Matrices." Materials 14, no. 22 (November 20, 2021): 7041. http://dx.doi.org/10.3390/ma14227041.

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Steady developments made in nanotechnology-based products have facilitated new perspectives for combating drug-resistant fungi. Silver nanoparticles represent one of the most attractive nanomaterials in biomedicine due to their exclusive optical, electromagnetic, and catalytic properties and antifungal potency compared with other metal nanoparticles. Most studies show that the physicochemical parameters affecting the antifungal potential of AgNPs include the shape, size, surface charge, and concentration and colloidal state. For the present study, pullulan (P) and its oxidized counterpart (PO) have been selected as matrices for the silver nanoparticles’ generation and stabilization (AgNPs). The TEMPO (2,2,6,6-tetramethylpiperidin-1-yl radical)–sodium hypochlorite–sodium bromide system was used for the C6 selective oxidation of pullulan in order to introduce negatively charged carboxylic groups in its structure. The structure and morphology of the synthesized AgNPs were analyzed using FTIR and EDX. The main objective of this study was to elucidate the antifungal activity of AgNPs on the clinical yeasts isolates and compare the performance of AgNPs with the conventional antifungals. In this study, different concentrations of AgNPs were tested to examine antifungal activity on various clinical isolates.

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