Academic literature on the topic 'Bioguided chemical study'

This study presents the bioguided chemical investigation of the 80% aqueous methanol extract of Geum urbanum aerial parts. Liquid–liquid partitioning of this extract in solvents of increasing polarity combined with biological screening showed that the ethyl acetate (EtOAc) soluble fraction was the most active part of the extract. This fraction was chemically profiled by a 13C nuclear magnetic resonance (NMR)-based dereplication method, resulting in the identification of 14 compounds. The dereplication process was followed by the purification of unknown and minor compounds of the EtOAc fraction. A new glycosylated phenol, namely, 3-(3,4-dihydroxyphenyl)propyl-α-l-rhamnopyranoside, together with 6 known compounds were isolated. Their structures were elucidated by spectroscopic methods including NMR and high-resolution electrospray ionization mass spectrometry. The antioxidant activity of fractions and isolated compounds were evaluated by 2,2,1-diphenyl-1-picrylhydrazyl and hydroxyl radical scavenging, and by cupric ion reducing antioxidant capacity assays. In parallel, their enzyme inhibitory property against human neutrophil elastase was assessed. Four subfractions, essentially containing polyphenols and triterpenes, exhibited a significant elastase inhibitory activity and an ellagitannin showed a very high radical scavenging activity.

Invasive plants efficiently colonize non-native territories, suggesting a great production of bioactive metabolites which could be effective antibiofilm weapons. Our study aimed to look for original molecules able to inhibit bispecies biofilm formed by S. aureus and C. albicans. Extracts from five invasive macrophytes (Ludwigia peploides, Ludwigia grandiflora, Myriophyllum aquaticum, Lagarosiphon major and Egeria densa) were prepared and tested in vitro against 24 h old bispecies biofilms using a crystal violet staining (CVS) assay. The activities of the extracts reducing the biofilm total biomass by 50% or more were comparatively analyzed against each microbial species forming the biofilm by flow cytometry (FCM) and scanning electron microscopy. Extracts active against both species were fractionated. Obtained fractions were analyzed by UHPLC-MS/MS and evaluated by the CVS assay. Chemical and biological data were combined into a bioactivity-based molecular networking (BBMN) to identify active compounds. The aerial stem extract of L. grandiflora showed the highest antibiofilm activity (>50% inhibition at 50 µg∙mL−1). The biological, chemical and BBMN investigations of its fractions highlighted nine ions correlated with the antibiofilm activity. The most correlated compound, identified as betulinic acid (BA), inhibited bispecies biofilms regardless of the three tested couples of strains (ATCC strains: >40% inhibition, clinical isolates: ≈27% inhibition), confirming its antibiofilm interest.

Objective: The objective of this research was to isolate and identify the major compound from the antioxidant extract obtained from the leaves of Bubonium graveolens.Methods: A bioguided fractionation was done to isolate and identify the major compound responsible of the antioxidant activity. The chemical structure of the isolated natural compound was established by spectroscopic means including UV, Fourier transform infrared, 1H NMR, and13C NMR. The purified compound was accurately tested for its antioxidant activity by the 2, 2-diphenyl-1-picrylhydrazyl assay at 517 nm.Results: The major compound named myricetin 3′-O-rhamnoside was isolated for the 1st time from the leaves of B. graveolens a medicinal specie of Algerian Sahara belonging to the Asteraceae family. The study showed that the myricetin 3ʹ-O-rhamnoside has an antioxidant potential 59% when compared with standard ascorbic acid with an IC 50=0.916 mg/ml.Conclusion: In the present work, it was possible to isolate and identify for the 1st time the major compound from the antioxidant fraction of B. graveolens.

The main challenge of plant chemical diversity exploration is how to develop tools to study exhaustively plant tissues. Their sustainable sourcing is a limitation as bioguided strategies and dereplication need quite large amounts of plant material. We examine if alternative solutions could overcome these difficulties by obtaining a secure, sustainable, and scalable source of tissues able to biosynthesize an array of metabolites. As this approach would be as independent of the botanical origin as possible, we chose eight plant species from different families. We applied a four steps culture establishment procedure, monitoring targeted compounds through mass spectrometry-based analytical methods. We also characterized the capacities of leaf explants in culture to produce diverse secondary metabolites. In vitro cultures were successfully established for six species with leaf explants still producing a diversity of compounds after the culture establishment procedure. Furthermore, explants from leaves of axenic plantlets were also analyzed. The detection of marker compounds was confirmed after six days in culture for all tested species. Our results show that the first stage of this approach aiming at easing exploration of plant chemodiversity was completed, and leaf tissues could offer an interesting alternative providing a constant source of natural compounds.

This study deals with the antimicrobial potential assessment ofUlva rigida,in regard to collection period and sampling site. Besides, we assess the chemical composition of bioactive compounds. For this purpose,Ulva rigidawas seasonally collected from two northern sites in Tunisia, Cap Zebib rocky shore (CZ) and Ghar El Melh lagoon (GEM). Crude organic extracts were prepared using dichloromethane and dichloromethane/methanol and tested against 19 indicator microorganisms using the disk diffusion method and microdilution technique to determine the minimum inhibitory concentration (MIC). Silica gel column and thin layer chromatography were used for purification of active compounds. Nuclear magnetic resonance (NMR) and gas chromatography were used for compounds identification. Samples ofUlva rigidacollected from the two sites have uniform antimicrobial activity throughout the year. Algae collected from the lagoon showed the largest spectrum of activity and were used for subsequent analysis. Bioguided purification of extracts fromUlva rigida,collected at GEM, leads to 16 active fractions with antibacterial effect mainly againstStaphylococcus aureusATCC 25923 andEnterococcus faecalisATCC 29212. These fractions were identified as fatty acids, mainly oleic (C18: 1 w9), linoleic (C18: 2 w6), palmitic (C16: 0), and stearic (C14: 0). MICs values ranged from 10 to 250μg/ml.

Abstract Tripodanthus acutifolius, commonly known as Jamillo, is an herbal remedy used in traditional Andean medicine to treat joint problems, such as sprains, dislocations, and rheumatic pain. This study aimed to evaluate the in vitro and in vivo anti-inflammatory and anti-arthritic activity of the aqueous extract and isolated compounds of T. acutifolius. A bioguided phytochemical analysis based on NMR/MS was performed to identify the compounds of the aqueous extract from T. acutifolius. The anti-inflammatory and anti-arthritic activity were evaluated by measuring inflammatory parameters (TNF-α, C-reactive protein, and fibrinogen) in murine models. The chemical structure determination led to the identification of four flavonoids: (E)-2’,4’-dihydroxy-6’-methoxy-chalcone (1), 6,2’,4’-trimethoxyflavone (2), 5,3’,4’-trihydroxy-6,7,8-trimethoxyflavone (3), and 5,4’-dihydroxy-6,7,8-trimethoxyflavone (4). All compounds inhibited the production of TNF-α in the RAW 264.7 cell line, with IC50 values of 0.78, 1.43, 5.73, and 9.71 μM, respectively. In addition, all flavonoids decreased the levels of TNF-α, C-reactive protein, and fibrinogen at a concentration of 5 mg/kg in murine models. Our research shows that these compounds isolated from T. acutifolius have anti-inflammatory and anti-arthritic properties, providing scientific evidence for the traditional use of this plant species.

Calotropis procera belongs to the Apocynaceae family and is found in the Northeast of Brazil. Several activities are attributed to this species, such as anti-inflammatory, antibacterial and anti-cancer activities. This research aimed to conduct a bioguided study of C. procera in order to isolate and identify triterpenes of the species and evaluate the cytotoxic activity of products of the plant species. The crude ethanolic extract (CEE) was obtained and partitioned. The hexanic phase was chromatographed giving the compound Cp-1, which was identified using spectroscopic techniques and thermal analysis. It was possible to identify Cp-1 as a triterpene called calotropenyl acetate, already reported in the literature. The cytotoxicity test was performed using the MTT technique and it was observed a good activity of CEE and hexanic phase against HL-60 and KS62 lines with an IC50 ranging between 26.8 ± 0.4 µg mL-1 and 47.0 ± 0.5 µg mL-1, besides no toxicity in normal lines, while Cp-1 showed no relevant activity against the tumor cells tested. The results indicated that the species contains in its chemical composition products with pharmacological interest, in addition to cytotoxic for leukemic cells, which can be further explored in complementary studies.

Buruli ulcer (BU) imposes a serious economic burden on affected households and on health systems that are involved in diagnosing the disease and treating patients. Research is needed to find cost-effective therapies for this costly disease. Plants have always been an important source of new pharmacologically active molecules. Consequently we decided to undertake the study of plants used in traditional treatment of BU in Benin and investigate their antimycobacterial activity as well as their chemical composition. Extracts from forty-four (44) plant species were selected on account of reported traditional uses for the treatment of BU in Benin and were assayed for antimycobacterial activities. Crude hydroethanolic extract from aerial parts ofHolarrhena floribunda(G. Don) T. Durand and Schinz was found to have significant antimycobacterial activity againstM.ulcerans(MIC = 125 µg/mL). We describe here the identification of four steroidal alkaloids fromMycobacterium ulceransgrowth-inhibiting fractions of the alkaloidal extract of the aerial parts ofHolarrhena floribunda. Holadysamine was purified in sufficient amount to allow the determination of its MCI (=50 µg/mL). These results give some support to the use of this plant in traditional medicine.

Bacteria of Streptomyces genus are a promising source of biologically active products, with applications in medicine, industry and agriculture. Therefore, the objective of this work was to evaluate the cytotoxic, antioxidant and antimicrobial activities of fermented rice extract and their semipurified fractions from Streptomyces spp. isolated of the rhizosphere of Paullinia cupana, Amazon-Brazil. For this, a bioguided study was carried out by the cytotoxic activity with methanolic extract of Streptomyces sp. ACTMS-12H UFPEDA 3405 (EMeOH-12H) partitioned with n-hexane, ethyl acetate and 2-butanol. The antioxidant activity was analyzed using the DPPH, ABTS and phosphomolybdenum methods, while the antimicrobial activity was investigated by microdilution method to determine the minimum inhibitory concentration (MIC) against species of bacteria and yeast. In the cytotoxicity test, the butanolic phase (FbuOH-12H) presented IC50 of 1.1 µg/mL against MOLT-4, with cell death probably by apoptosis, but did not cause cytotoxicity on peripheral blood mononuclear cell (PBMC) or human erythrocytes. Chemical prospecting detected the presence of saponins and reducing sugars on 2-butanol fraction (FBuOH-12H), which can be related to cytotoxicity. On the antioxidant activity by ABTS, the partition with ethyl acetate (FAcOEt-12H) showed antioxidant capacity of 1161.7 ± 0.04 µM of Trolox/g of extract, indicating an expressive reactivity of the phase with this radical. The aqueous phases (from hexane, ethyl acetate and methanol extracts) were active in all tested microorganisms, except E. faecalis.

ABSTRACTIn the current work we performed a review of the Araceae family species traditionally used to treat malaria and its symptoms. The aim is to reveal the large number of antimalarial Araceae species used worldwide and their great unexplored potential as sources of antimalarial natural products. The SciFinder Scholar, Scielo, PubMed, ScienceDirect and Google books search engines were consulted. Forty-three records of 36 species and 23 genera of Araceae used for malaria and symptoms treatment were found. The neotropical genera Philodendron Schott and Anthurium Schott were the best represented for the use in the treatment of malaria, fevers, liver problems and headaches. Leaves and tubers were the most used parts and decoction was the most common preparation method. The extracts of Araceae species inhibit the in vitro growth of the human malaria parasite, the Plasmodium falciparum Welch, and significant median inhibitory concentrations (IC50) for extracts of guaimbê-sulcado (Rhaphidophora decursiva (Roxb.) Schott), aninga (Montrichardia linifera (Arruda) Schott), Culcasia lancifolia N.E. Br. and forest anchomanes (Anchomanes difformis (Blume) Engl.) have been reported demonstrating the antimalarial and cytotoxicity potential of the extracts and sub-fractions. In the only report about the antimalarial components of this family, the neolignan polysyphorin and the benzoperoxide rhaphidecurperoxin presented strong in vitro inhibition of the D6 and W2 strains of Plasmodiumfalciparum (IC50 = 368-540 ng/mL). No live study about antimalarial activity in animal models has been conducted on a species of Araceae. More bioguided chemical composition studies about the in vitro and also thein vivo antimalarial activity of the Araceae are needed in order to enhance the knowledge about the antimalarial potential of this family.

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico
Este trabalho descreve: 1) sÃntese quimioenzimÃtica de Ãsteres do cloranfenicol (1) e tianfenicol (2), utilizando lipases como fonte biocatalÃtica; 2) avaliaÃÃo do potencial atitumoral de fungos marinhos isolados da ascÃdia Eudistoma vannamei. Na primeira parte, realizou-se a sÃntese enzimÃtica de dois derivados monoacilados do cloranfenicol (1), atravÃs de reaÃÃes de hidrÃlise de derivados diacilados, e oito derivados monoacilados do tianfenicol (2), pela acilaÃÃo e hidrÃlise enzimÃtica do tianfenicol e derivados diacilados, respectivamente. Os seguintes parÃmetros foram variados: enzima, solvente, temperatura, pH e proporÃÃo entre solvente e agente hidrolÃtico e, na hidrÃlise enzimÃtica dos derivados de cloranfenicol diacilados, os melhores resultados foram com a mistura de CH3CN:tampÃo fosfato (pH 7) na proporÃÃo de 20:80, CAL-B como biocatalisador, temperatura de 20 ÂC, agitaÃÃo de 250 rpm e tempo reacional de 24 h. A reaÃÃo de acilaÃÃo enzimÃtica do tianfenicol (2), utilizando CAL-B como biocatalisador e Ãsteres vinÃlicos como doadores de grupos acila, se mostrou bastante eficiente, com altos Ãndices de conversÃo e seletividade. Os processos forneceram unicamente os produtos de acilaÃÃo da hidroxila menos impedida (3â-OH). A eficiÃncia da enzima CAL-B reciclada na reaÃÃo de acilaÃÃo do tianfenicol (2) foi investigada, sendo possÃvel concluir que esta se mantÃm ativa durante os cinco processos reacionais testados. A hidrÃlise enzimÃtica dos derivados diacilados do tianfenicol forneceu, majoritariamente, os produtos de hidrÃlise na posiÃÃo 3. Na segunda parte do trabalho, foram isoladas 11 cepas fÃngicas (EV1 a EV11) da ascÃdia E. vannamei, as quais foram cultivadas em meio lÃquido BD (batata-dextrose) com objetivo de realizar um estudo bioguiado atravÃs da avaliaÃÃo da atividade citotÃxica de seus extratos e fraÃÃes. Foram ensaiados os extratos acetoetÃlico do meio lÃquido e metanÃlico do micÃlio, previamente separados. Os extratos mais ativos foram os oriundos de EV10 e EV11, os quais foram identificados como Aspergillus sp. por anÃlise molecular. O fungo EV10 foi cultivado em grande escala para fracionamento bioguiado e isolamento dos metabÃlitos secundÃrios bioativos. Foi possÃvel isolar quatro micotoxinas: meleÃna, cis-4-hidroximeleÃna, trans-4-hidroximeleÃna e Ãcido penicÃlico, dentre as quais, somente o Ãcido penicÃlico foi identificado como responsÃvel pela atividade do extrato.
This work describes: 1) chemoenzymatic synthesis of chloramphenicol (1) and thiamphenicol (2) esters, using lipases as biocatalyst source; 2) investigation of the antitumor potential of fungi isolated from the marine ascidian Eudistoma vannamei. In the first part, it was carried out the enzymatic synthesis of two monoacyl derivatives of chloramphenicol (1), through the hydrolysis of the diacyl derivatives, and eight monoacyl derivatives of thiamphenicol (2), by the enzymatic acylation and hydrolysis of thiamphenicol and diacyl derivatives, respectively. The following p arameters were varied: enzyme, solvent, temperature, pH and proportion between solvent and agent hydrolytic, and in enzymatic hydrolysis of the diacyl derivatives of chloramphenicol, the best results were reached when using a mixture of CH3CN: phosphate buffer (pH 7) in the proportion 20:80, CAL-B as biocatalyst, temperature of 20 Â C, 250 rpm and reaction time of 24 h. The enzymatic acylation of thiamphenicol (2), using CAL-B as biocatalyst and vinyl esters as acyl donor groups, was very efficient, with high conversion and selectivity. The processes provided only products of the ac ylation of the less hindered hydroxyl group (3'-OH). The efficiency of the recycled CAL-B in the acylation of thiamphenicol (2) was investigated, being possible to conclude that its activity was maintained during the five tested reactions. Enzymatic hydrolysis of diacylated derivatives of thiamphenicol, provided mostly the hydrolysis products in position 3. In the second part of this work, we isolated 11 fungal strains (EV1 to EV11) associated to the ascidian E. vannamei, which were cultivated in liquid BD (potato dextrose) in order to conduct a bioguided study by evaluating the cytotoxic activity of their extracts and fractions. The ethylacetate extracts of the liquid medium and methanol extracts from the mycelium, previously separate, were assayed and the most active extracts were those from EV10 and EV11, which were identified as Aspergillus sp. by molecular analysis. EV10 was grown on a larger scale allowing the bioguided fractionation and isolation of bioactive secondary metabolites. It was possible to isolate four mycotoxins: mellein, cis-4-hydroxymellein, trans-4-hydroxymellein and penicillic acid, among which only the later compound was identified as responsible for the activity of the extract.

Ce travail présente l’étude phytochimique bioguidée de neuf plantes ivoiriennes présélectionnées pour leur potentielle activité antiparasitaire et/ou fongicide : Combretum micranthum G. Don (Combretaceae), Elaeis guineensis Jacq. (Arecaceae), Erigeron floribundus Kunth Sch.Bip (Asteraceae), Oldfieldia africana Benth. & Hook. f. (Euphorbiaceae), Octoknema borealis Hutch. & Dalziel (Olacaceae), Omphalocarpum ahia A. Chev. (Sapotaceae), Omphalocarpum elatum Miers (Sapotaceae), Tristemma coronatum Benth. (Melastomataceae) et Tristemma spp (Melastomataceae).Des extractions séquentielles ont conduit à quarante-quatre extraits bruts, qui ont été par la suite criblés in vitro à 25 µg/ml contre Toxoplasma gondii. Trente-sept extraits se sont avérés non cytotoxiques contre les cellules Véro et parmi eux, dix inhibaient plus de 50% la croissance parasitaire. D’un autre côté, le criblage de ces quarante-quatre extraits a révélé que cinq d’entre eux inhibaient plus de 50% de la croissance de Candida auris et d’autres souches de levures.Trois extraits qui inhibaient plus de 90% de la croissance parasitaire ont été sélectionnés pour l’identification des composés en présence, responsables de l’activité contre T. gondii : l’extrait Dichlorométhane des écorces du tronc et l’extrait AcOEt des feuilles de Omphalocarpum ahia ; et l’extrait hydrométhanolique des feuilles de E. guineensis. Les travaux réalisés sur les écorces et les feuilles de O. ahia ont conduit majoritairement à des triterpènes, dont huit nouveaux, sur lesquels une chimiosensibilité a été réalisée. Celle-ci montre qu’un triterpène de type ursane inhibe fortement la croissance du toxoplasme, tout en étant très sélectif à celui-ci. L’indice de sélectivité et la CI50 nous ont permis de discuter la relation structure-activité (SRA) entre les triterpènes isolés. La cible biologique sur le toxoplasme a été recherchée par Docking inverse, les résultats ont indiqué que certains triterpènes bioactifs forment différents complexes avec la protéine de liaison à l’ADN de la famille des histones, la protéine contenant le domaine SET et la protéine contenant le domaine pH du toxoplasme.Le fractionnement bioguidé de l’extrait hydrométhanolique des feuilles de E. guineensis n’a pas permis de retrouver l’activité antitoxoplasmique. La purification des fractions a permis de caractériser des triterpènes, des sesquiterpènes (dont trois nouveaux), des polyphénols (dont un nouveau), des flavonoïdes et d’alcaloïde qui sont potentiellement responsables de l’activité antitoxoplasmique masquée.L’extrait AcOEt des écorces du tronc de Octoknema borealis est le seul à avoir montré une activité antifongique contre toutes les levures (CMI = 25 µg/ml) et plus de 70% à 90% d’inhibition de la croissance de C. auris et des autres levures. Cet extrait AcOEt a été fractionné par CPC, et l’activité antifongique est retrouvée dans la majorité de ses fractions. Le profilage chimique de ses fractions a été effectuée par déréplication en RMN 13C (CaraMel) et nous a permis d’identifier les métabolites responsables de cette forte activité fongicide
This work presents a bioguided phytochemical study of nine Ivorian plants pre-selected for their potential antiparasitic and/or fungicidal activity: Combretum micranthum G. Don (Combretaceae), Elaeis guineensis Jacq. (Arecaceae), Erigeron floribundus Kunth Sch.Bip (Asteraceae), Oldfieldia africana Benth. & Hook. f. (Euphorbiaceae), Octoknema borealis Hutch. & Dalziel (Olacaceae), Omphalocarpum ahia A. Chev (Sapotaceae), Omphalocarpum elatum Miers (Sapotaceae), Tristemma coronatum Benth (Melastomataceae) and Tristemma spp (Melastomataceae).Sequential extractions yielded forty-four crude extracts, which were then screened in vitro at 25 µg/ml against Toxoplasma gondii. Thirty-seven extracts were found to be non-cytotoxic against Vero cells, and ten of these inhibited parasite growth by more than 50%. On the other hand, screening of these forty-four extracts revealed that five of them inhibited more than 50% of the growth of Candida auris and other yeast strains.Three extracts that inhibited more than 90% of parasite growth were selected for the identification of the compounds present, responsible for the activity against T. gondii: the Dichloromethane extract of the bark of the trunk and the AcOEt extract of the leaves of Omphalocarpum ahia; and the hydromethanolic extract of the leaves of E. guineensis.The work carried out on the barks and leaves of O. ahia led mainly to the discovery of triterpenes, including eight new ones, for which chemosensitivity tests were carried out. This showed that an ursan-type triterpene strongly inhibits the growth of toxoplasma, while being highly selective to it. The selectivity index and IC50 allowed us to discuss the structure-activity relationship (SAR) between the isolated triterpenes. The biological target on toxoplasma was sought by reverse docking, and the results indicated that certain bioactive triterpenes form different complexes with the DNA-binding protein of the histone family, the protein containing the SET domain and the protein containing the pH domain of toxoplasma.Bioguided fractionation of the hydromethanolic extract of E. guineensis leaves did not reveal any antitoxoplasmic activity. Purification of the fractions enabled us to characterise triterpenes, sesquiterpenes (including three new ones), polyphenols (including one new one), flavonoids and alkaloids that are potentially responsible for the masked antitoxoplasmic activity.The AcOEt extract of Octoknema borealis trunk bark was the only one to show antifungal activity against all yeasts (MIC = 25 µg/ml) and over 70% to 90% growth inhibition of C. auris and other yeasts. This AcOEt extract was fractionated by CPC, and antifungal activity was found in the majority of its fractions. The chemical profiling of these fractions was carried out by 13C NMR dereplication (CaraMel) and enabled us to identify the metabolites responsible for this strong fungicidal activity