Добірка наукової літератури з теми "Curcumine – Analogues"
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся зі списками актуальних статей, книг, дисертацій, тез та інших наукових джерел на тему "Curcumine – Analogues".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Статті в журналах з теми "Curcumine – Analogues":
1
Al-Asadi, Ali M., Salah S. Al-Luaibi, Basil A. Saleh, Mohammed A. Baashen, and Gamal A. El-Hiti. "Antioxidant Properties of Curcumin Analogues to Inhibit Thermal Degradation of Low-Density Polyethylene: Experimental and DFT Study." Journal of Chemistry 2022 (June 20, 2022): 1–6. http://dx.doi.org/10.1155/2022/5391296.
Анотація:
Curcumin can be isolated from plants (Curcuma longa) and it belongs to the ginger family. It exhibits many useful properties and acts as an antioxidant. The aim of the current study was to prepare eight curcumin analogues and investigate their antioxidant activities to inhibit the thermal degradation of low-density polyethylene (LDPE). The carbonyl index (CI) was measured to test the effectiveness of the curcumin analogues. Various doses (0.5, 1, 2, 4, and 6% wt/wt) of a mixture containing LDPE and curcumin analogues were prepared, and the CI was measured. The eight curcumin analogues were found to have good to excellent antioxidant activity against the degradation of LDPE. It was clear that the curcumin analogue derived from vanillin and acetone has the highest antioxidant activity. The density functional theory study was conducted for the eight curcumin analogues to test their reactivity and stability. Again, the global reactivity descriptors analysis showed that compound derived from vanillin and acetone was the most reactive compound to inhibit thermal degradation of LDPE.
2
Nocito, Marta Claudia, Arianna De Luca, Francesca Prestia, Paola Avena, Davide La Padula, Lucia Zavaglia, Rosa Sirianni, et al. "Antitumoral Activities of Curcumin and Recent Advances to ImProve Its Oral Bioavailability." Biomedicines 9, no. 10 (October 14, 2021): 1476. http://dx.doi.org/10.3390/biomedicines9101476.
Анотація:
Curcumin, a main bioactive component of the Curcuma longa L. rhizome, is a phenolic compound that exerts a wide range of beneficial effects, acting as an antimicrobial, antioxidant, anti-inflammatory and anticancer agent. This review summarizes recent data on curcumin’s ability to interfere with the multiple cell signaling pathways involved in cell cycle regulation, apoptosis and the migration of several cancer cell types. However, although curcumin displays anticancer potential, its clinical application is limited by its low absorption, rapid metabolism and poor bioavailability. To overcome these limitations, several curcumin-based derivatives/analogues and different drug delivery approaches have been developed. Here, we also report the anticancer mechanisms and pharmacokinetic characteristics of some derivatives/analogues and the delivery systems used. These strategies, although encouraging, require additional in vivo studies to support curcumin clinical applications.
3
Yi, Yau Xin, Anand Gaurav, and Gabriel A. Akowuah. "Docking Studies of Curcumin and Analogues with Various Phosphodiesterase 4 Subtypes." Current Drug Discovery Technologies 17, no. 2 (June 19, 2020): 248–60. http://dx.doi.org/10.2174/1570163815666181017091655.
Анотація:
Introduction: The primary aim of this study is to understand the binding of curcumin and its analogues to different PDE4 subtypes and identify the role of PDE4 subtype inhibition in the anti-inflammatory property of curcumin. Docking analysis has been used to acquire the above mentioned structural information and this has been further used for designing of curcumin derivatives with better anti-inflammatory activity. Materials and Methods: Curcumin and its analogues were subjected to docking using PDE4A, PDE4B, PDE4C and PDE4D as the targets. A data set comprising 18 analogues of curcumin, was used as ligands for docking of PDE4 subtypes. Curcumin was used as the standard for comparison. Docking was performed using AutoDock Vina 1.1.2 software integrated in LigandScout 4.1. During this process water molecules were removed from proteins, charges were added and receptor structures were minimised by applying suitable force fields. The docking scores were compared, and the selectivity of compounds for PDE4B over PDE4D was calculated as well. Results: All curcumin analogues used in the study showed good binding affinity with all PDE4 subtypes, with evident selectivity towards PDE4B subtype. Analogue A11 provides the highest binding affinity among all ligands. Conclusion: Curcumin and analogues have moderate to strong affinity towards all PDE4 subtypes and have evident selectivity towards PDE4B. The Oxygen atom of the methoxy group plays a key role in PDE4B binding and any alterations could interfere with the binding. Tetrahydropyran side chain and heterocyclic rings are also suggested to be helpful in PDE4B binding.
4
Cheng, Yatian, Jian Zhang, Yan Shao, Yixiang Xu, Haixia Ge, Boyang Yu, and Weiwei Wang. "Enzyme-Catalyzed Glycosylation of Curcumin and Its Analogues by Glycosyltransferases from Bacillus subtilis ATCC 6633." Catalysts 9, no. 9 (August 29, 2019): 734. http://dx.doi.org/10.3390/catal9090734.
Анотація:
Curcumin is a naturally occurring polyphenolic compound that is commonly used in both medicine and food additives, but its low aqueous solubility and poor bioavailability hinder further clinical applications. For assessing the effect of the glycosylation of curcumin on its aqueous solubility, two glycosyltransferase genes (BsGT1 and BsGT2) were cloned from the genome of the strain Bacillus subtilis ATCC 6633 and over-expressed in Escherichia coli. Then, the two glycosyltransferases were purified, and their glycosylation capacity toward curcumin and its two analogues was verified. The results showed that both BsGT1 and BsGT2 could convert curcumin and its two analogues into their glucosidic derivatives. Then, the structures of the derivatives were characterized as curcumin 4′-O-β-D-glucoside and two new curcumin analogue monoglucosides namely, curcumoid-O-α-D-glucoside (2a) and 3-pentadienone-O-α-D-glucoside (3a) by nuclear magnetic resonance (NMR) spectroscopy. Subsequently, the dissolvability of curcumin 4′-O-β-D-glucoside was measured to be 18.78 mg/L, while its aglycone could not be determined. Furthermore, the optimal catalyzing conditions and kinetic parameters of BsGT1 and BsGT2 toward curcumin were determined, which showed that the Kcat value of BsGT1 was about 2.6-fold higher than that of BsGT2, indicating that curcumin is more favored for BsGT2. Our findings effectively apply the enzymatic approach to obtain glucoside derivatives with enhanced solubility.
5
Muhammad, Imran, Nadeem Muhammad, Khan Muhammad Asif, Ahmed Sheraz, Imran Ali, Amir Rai Muhammad, Arshad Muhammad Umair, et al. "Curcumin and its allied analogues: epigenetic and health perspectives – a review." Czech Journal of Food Sciences 35, No. 4 (August 30, 2017): 285–310. http://dx.doi.org/10.17221/584/2015-cjfs.
Анотація:
Curcumin (diferuoyl methane) is a yellow active ingredient present in turmeric. It is a homodimer of feruloylmethane that comprises a hydroxyl and methoxy group (heptadiene with two Michael acceptors), and α-, β-diketone. It contains various metabolites, i.e. hexahydrocurcumin (HHC), tetrahydrocurcumin (THC), octahydrocurcumin (OHC), dihydrocurcumin (DHC), curcumin sulphate, and curcumin glucuronide. Curcumin has been proven the most effective histone deacetylase (HDAC) inhibitor in HeLa nuclear extracts. It has the ability to affect the Akt, growth factors, NF-kB, and metastatic and angiogenic pathways. Curcumin has a strong therapeutic or preventive potential against several major human ailments, i.e. suppression of inflammation, cardiovascular, diabetes, tumorigenesis, chronic fatigue, antidepressant and neurological activities, depression, loss of muscle and bone, and neuropathic pain. In future, higher utilisation of curcumin as an active agent in food based products is required to curtail the human health disorders.
6
Athipornchai, Anan, Nattisa Niyomtham, Wachirachai Pabuprapap, Vachiraporn Ajavakom, Maria Duca, Stéphane Azoulay, and Apichart Suksamrarn. "Potent Tyrosinase Inhibitory Activity of Curcuminoid Analogues and Inhibition Kinetics Studies." Cosmetics 8, no. 2 (May 4, 2021): 35. http://dx.doi.org/10.3390/cosmetics8020035.
Анотація:
Natural tyrosinase inhibitors from herbal plants are promising therapeutic agents for skincare and cosmetic products. Natural curcuminoids exhibit weak antityrosinase properties. The structural modification of curcumin, the major curcuminoid from Curcuma longa, gave 14 analogues. The tyrosinase inhibitory activity of the natural curcuminoids and the modified analogues on both L-tyrosine and DOPA substrates were evaluated. The inhibition kinetics were also undertaken. For analogues with potent activity on the L-tyrosine substrate, the isoxazole analogue 12 and two reduced analogues, hexahydrocurcumin (16) and the α,β-unsaturated analogue 17, showed IC50 values of 8.3, 14.6 and 9.4 µM, and were 20.9-, 11.9- and 18.4-fold more active, respectively, than kojic acid, the reference compound. For the analogues with potent antityrosinase on DOPA substrate, the dimethylated analogue 5 exhibited the strongest antityrosinase activity against the DOPA substrate, with the IC50 value of 8.0 µM, which was 16.6-fold more active than kojic acid. The inhibition kinetics revealed that curcuminoid 5 could bind with both free enzyme and with the enzyme–substrate complex. It acted as a competitive–uncompetitive mixed-II type inhibitor. Curcuminoid 17 could bind with both free enzyme and the enzyme–substrate complex. The results indicated that 17 acted as a competitive–uncompetitive mixed-I type inhibitor, while curcuminoid 12 was a noncompetitive inhibitor which bound with both free enzymes and the enzyme–substrate complex. These potent analogues might serve as new potential tyrosinase inhibitors for the prevention and treatment of skin pigmentation disorders.
7
Morais de Lima, Ednilza, Gabriel Antônio dos Santos, Khaled Hayek, José Jardes Da Gama Bitencourt, and Carolina Passarelli Gonçalves. "Biossíntese Dirigida pelo Precursor de Curcumina pela Curcuma longa L." Ensaios e Ciência C Biológicas Agrárias e da Saúde 25, no. 3 (September 29, 2021): 357–60. http://dx.doi.org/10.17921/1415-6938.2021v25n3p357-360.
Анотація:
O composto (E,E)-1,7-bis(4-hidroxi-3-metoxifenil)-1,6-heptadieno-3,5-diona, conhecido popularmente como curcumina, é um composto fitoquímico encontrado nos rizomas da Curcuma longa L. Esta substância já demonstrou diversas atividades terapêuticas importantes, como anti-inflamatória, antioxidante, antibacteriana, antiviral e antitumoral, por exemplo. Entretanto, apesar de ser o composto majoritário da via biossintética da Curcuma longa L. é descrito que apenas de 2 a 8% do peso total do rizoma, corresponde à quantidade de curcumina que pode ser extraída. Com o objetivo de estimular a biossíntese da curcumina, este trabalho utilizou a biossíntese dirigida por precursores, que combina síntese química com transformações enzimáticas naturais, e permite que materiais de partida não nativos sejam incorporados às vias biossintéticas. Utilizando essa abordagem foi estabelecido um sistema in vitro de cultura do rizoma suplementado com o precursor, ácido ferúlico e dois análogos. Os dois análogos sintetizados são sais de potássio solúveis em água e foram obtidos com alto grau de pureza e rendimentos consideráveis. A incorporação de diferentes concentrações do precursor e seus análogos ocasionou, em algumas concentrações, um aumento de até 40% da biossíntese da curcumina. O método desenvolvido, validado, utiliza a espectroscopia UV/VIS para quantificar as concentrações de curcumina, através da análise de seus extratos alcoólicos, nos extratos obtidos a partir dos rizomas suplementados. Palavras-chave: Curcumina. Rizoma. Biossíntese Dirigida pelo Precursor. Ácido Ferúlico. Sais Potássicos. Abstract The compound (E,E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, popularly known as curcumin, is a phytochemical found in the rhizomes of Curcuma longa L. This substance has already demonstrated several important therapeutic activities, such as anti-inflammatory, antioxidant, antibacterial, antiviral and antitumor, for example. However, despite being the major compound of the Curcuma longa L. biosynthetic pathway, it is described that only from 2 to 8% of the total weight of the rhizome corresponds to the amount of curcumin that can be extracted. In order to stimulate the curcumin biosynthesis, this work used the precursor-directed biosynthesis, which combines chemical synthesis with natural enzymatic transformations, and allows that non-native starting materials to be incorporated into the biosynthetic pathways. Using this approach, an in vitro rhizome culture system supplemented with the precursor, ferulic acid and two analogs was established. The two synthesized analogs are water-soluble potassium salts and were obtained with a high degree of purity and considerable yields. The incorporation of different precursor concentrations and its analogues caused, in some concentrations, an increase of up to 40% in curcumin biosynthesis. The method was developed, validated, and uses UV/VIS spectroscopy to quantify curcumin concentrations, through the analysis of its alcoholic extracts, in extracts obtained from supplemented rhizomes. Keywords: Curcumin. Rhizome. Precursor-Directed Biosynthesis. Ferulic Acid. Potassium Salts.
8
R, Thirumalaisamy. "Comparative Anti–Alzheimer’s Potential Evaluation of Curcumin and Curcumin Analogues obtained from ZINC Database: An in-Silico Validation." TEXILA INTERNATIONAL JOURNAL OF PUBLIC HEALTH 9, no. 4 (December 28, 2021): 269–83. http://dx.doi.org/10.21522/tijph.2013.09.04.art023.
Анотація:
Curcumin and its eleven analogues obtained from the ZINC database were screened for its anti-Alzheimer’s potential validated through in silico approach. Curcumin, eleven curcumin analogues from the ZINC database, and six standard anti-Alzheimer’s drugs were obtained from SWISS ADME and Pub chem database. All obtained molecules were subjected to drug-likeness, molecular docking, and ADMET analysis. Curcumin and eleven curcumin analogues show no violations against five drug-likeness rules, whereas 2 standard drugs (CID¬_11269353, CID_46883536) out of 5 screened standard drug molecules shows violations in drug likeness property. Curcumin and curcumin analogues possess docking scores in the range of -7.5 to 9.9 Kcal/mol, whereas reference standard drugs docking score lies in the range of -6.4 to -11.0 Kcal/mol against all three Alzheimer’s disease molecular targets. Finally, our present study has proven that curcumin analogues possess some novel anti-Alzheimer’s properties over curcumin and standard reference drug. It needs to be validated and commercialized after in vivo preclinical trials.
9
Ahsan, Mohamed Jawed, Kavita Choudhary, Amena Ali, Abuzer Ali, Faizul Azam, Atiah H. Almalki, Eman Y. Santali, Md Afroz Bakht, Abu Tahir, and Salahuddin. "Synthesis, DFT Analyses, Antiproliferative Activity, and Molecular Docking Studies of Curcumin Analogues." Plants 11, no. 21 (October 25, 2022): 2835. http://dx.doi.org/10.3390/plants11212835.
Анотація:
With 19.3 million new cases and almost 10 million deaths in 2020, cancer has become a leading cause of death today. Curcumin and its analogues were found to have promising anticancer activity. Inspired by curcumin’s promising anticancer activity, we prepared three semi-synthetic analogues by chemically modifying the diketone function of curcumin to its pyrazole counterpart. The curcumin analogues (3a–c) were synthesized by two different methods, followed by their DFT analyses to study the HOMO/LUMO configuration to access the stability of compounds (∆E = 3.55 to 3.35 eV). The curcumin analogues (3a–c) were tested for antiproliferative activity against a total of five dozen cancer cell lines in a single (10 µM) and five dose (0.001 to 100 µM) assays. 3,5-Bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(phenoxy)ethanone (3b) and 3,5-bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(2,4-dichlorophenoxy)ethanone (3c) demonstrated the most promising antiproliferative activity against the cancer cell lines with growth inhibitions of 92.41% and 87.28%, respectively, in a high single dose of 10 µM and exhibited good antiproliferative activity (%GIs > 68%) against 54 out of 56 cancer cell lines and 54 out of 60 cell lines, respectively. The compound 3b and 3c demonstrated the most potent antiproliferative activity in a 5-dose assay with GI50 values ranging between 0.281 and 5.59 µM and 0.39 and 0.196 and 3.07 µM, respectively. The compound 3b demonstrated moderate selectivity against a leukemia panel with a selectivity ratio of 4.59. The HOMO-LUMO energy-gap (∆E) of the compounds in the order of 3a > 3b > 3c, was found to be in harmony with the anticancer activity in the order of 3c ≥ 3b > 3a. Following that, all of the curcumin analogues were molecular docked against EGFR, one of the most appealing targets for antiproliferative activity. In a molecular docking simulation, the ligand 3b exhibited three different types of interactions: H-bond, π-π-stacking and π-cationic. The ligand 3b displayed three H-bonds with the residues Met793 (with methoxy group), Lys875 (with phenolic group) and Asp855 (with methoxy group). The π-π-stacking interaction was observed between the phenyl (of phenoxy) and the residue Phe997, while π-cationic interaction was displayed between the phenyl (of curcumin) and the residue Arg841. Similarly, the ligand 3c displayed five H-bonds with the residue Met793 (with methoxy and phenolic groups), Lys845 (methoxy group), Cys797 (phenoxy oxygen), and Asp855 (phenolic group), as well as a halogen bond with residue Cys797 (chloro group). Furthermore, all the compound 3a–c demonstrated significant binding affinity (−6.003 to −7.957 kcal/mol) against the active site of EGFR. The curcumin analogues described in the current work might offer beneficial therapeutic intervention for the treatment and prevention of cancer. Future anticancer drug discovery programs can be expedited by further modifying these analogues to create new compounds with powerful anticancer potentials.
10
Chen, Jian, Linlin Zhang, Yilai Shu, Liping Chen, Min Zhu, Song Yao, Jiabing Wang та ін. "Curcumin Analogue CA15 Exhibits Anticancer Effects on HEp-2 Cells via Targeting NF-κB". BioMed Research International 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/4751260.
Анотація:
Laryngeal carcinoma remains one of the most common malignancies, and curcumin has been proven to be effective against head and neck cancers in vitro. However, it has not yet been applied in clinical settings due to its low stability. In the current study, we synthesized 34 monocarbonyl analogues of curcumin with stable structures. CA15, which exhibited a stronger inhibited effect on laryngeal cancer cells HEp-2 but a lower toxicity on hepatic cells HL-7702 in MTT assay, was selected for further analysis. The effects of CA15 on cell viability, proliferation, migration, apoptosis, and NF-κB activation were measured using MTT, Transwell migration, flow cytometry, Western blot, and immunofluorescence assays in HEp-2 cells. An NF-κB inhibitor, BMS-345541, as well as curcumin was also tested. Results showed that CA15 induced decreased toxicity towards HL-7702 cells compared to curcumin and BMS-345541. However, similar to BMS-345541 and curcumin, CA15 not only significantly inhibited proliferation and migration and induced caspase-3-dependent apoptosis but also attenuated TNF-α-induced NF-κB activation in HEp-2 cells. These results demonstrated that curcumin analogue CA15 exhibited anticancer effects on laryngeal cancer cells via targeting of NF-κB.
Дисертації з теми "Curcumine – Analogues":
1
Jourdan, Jean-Pierre. "Conception, synthèse et évaluation biologique de nouveaux analogues de la curcumine : potentiels agents pléiotropes d'intérêt thérapeutique dans la maladie d'Alzheimer." Caen, 2015. http://www.theses.fr/2015CAEN4012.
Анотація:
La maladie d’Alzheimer, forme la plus commune des démences séniles, est une maladie progressive, chronique, neurodégénérative et irréversible. Les causes physiopathologiques de cette démence sont nombreuses. Parmi elles on peut citer l’agrégation de peptides β-amyloïdes, l’hyperphosphorylation de la protéine Tau, l’inflammation neuronale et le stress oxydatif. Une des approches thérapeutiques récemment développées pour modifier l’évolution de cette maladie multifactorielle est la conception de ligands multicibles. On trouve dans la nature des molécules douées de telles fonctions, dont la curcumine. C’est un polyphénol naturel extrait de la plante Curcuma longa L. Et elle peut être considérée comme un principe actif d’intérêt dans le traitement de la maladie d’Alzheimer, car elle possède des propriétés inhibitrices de l’agrégation β-amyloïde, antioxydantes et anti-inflammatoires. Elle souffre cependant d’une mauvaise biodisponibilité et ne peut être utilisée en thérapeutique. C’est la raison pour laquelle nous avons conçu des analogues de la Curcumine en série pyrrolizinone et aminoindanone en tant que potentiels ligands multicibles d’intérêt dans le traitement de la maladie d’Alzheimer. Dans ce manuscrit, est décrite la démarche de drug design mêlant la pharmacochimie, la modélisation moléculaire et les évaluations biologiques menant à la conception et à la pharmacomodulation de ces analogues. Enfin, une étude préliminaire de la drugabilité des composés néosynthétisés est présentéeAlzheimer's disease, the most common form of elderly dementia in the world, is a progressive, chronic, degenerative and irreversible disease. They are many pathophysiological causes of dementia, among them there may be mentioned β-aggregation of amyloid peptides, tau protein hyperphosphorylation, neuronal inflammation and oxidative stress. A recently developed therapeutic approach to modify the evolution of this multifactorial disease is the design of multi-target directed ligands. In the nature, there are molecules with such functions like curcumin. It’s a natural polyphenol extracted from the plant Curcuma longa L. And it can be considered as an active product useful in the treatment of Alzheimer's disease because of its inhibitory properties of β-amyloid aggregation, antioxidant and inflammatory inhibition activities. However, it suffers from poor bioavailability and can’t be used in therapy. That's why we designed novel curcumin analogs in pyrrolizinone and aminoindanone series as potential multi-target ligands potentially useful in the treatment of Alzheimer's disease. In this manuscript, is described the drug design approach combining medicinal chemistry, molecular modeling and biological assessments leading to these analogues. Finally, a preliminary drugability study of the newly synthesized compounds is presented
2
Pecourneau, Jérémy. "Réponses photoinduites d'analogue biomimétique de la cyclocurcumine : vers des thérapies assistées par la lumière." Electronic Thesis or Diss., Université de Lorraine, 2022. http://www.theses.fr/2022LORR0205.
Анотація:
Au-delà de la thérapie photodynamique (PDT), il existe plusieurs alternatives thérapeutiques assistées par la lumière parmi lesquelles la thérapie photothermique (PTT) ou encore la photoisomérisation dont l’action mécanique induirait des dommages cellulaires au sein des membranes. De plus, les molécules capables d’absorber simultanément deux photons permettraient de surmonter la nécessité d’une excitation à haute énergie par photon tout en gardant une pénétration suffisante des tissus. Dans ce contexte, nous nous sommes intéressés à la conception et à l’étude d’analogues biomimétiques de la cyclocurcumine (CC), un photoswitch E/Z naturel. Guidé par la modélisation moléculaire, ces nouveaux composés de type donneur-accepteur ont été structurellement conçus pour accroître la section efficace d'absorption à deux photons (σ2). Dans un premier temps, nous avons synthétisé deux classes d’analogues de la CC portant des groupements accepteurs (oxo et malonitrile) et donneurs (hydroxy, alcoxy et amine) ainsi qu’un bras PEG pour augmenter leur hydrophilie. Libres en solution, les dérivés oxo subissent une isomérisation photoinduite réversible, sans aucune isomérisation thermique en retour dans l’obscurité alors que les dérivés malonitrile ne photocommutent plus mais subissent une relaxation vibrationnelle. Elle conduit ainsi à une augmentation de température, d’intérêt en thérapie photothermique. Enfin, confinées dans un environnement lipidique (bicouches de liposomes et monocouches de Langmuir), la cinétique d’isomérisation directe E→Z des composés oxo est fortement ralentie et aucune isomérisation retour Z→E n’est observée, ni thermique ni sous illumination. Ces mêmes composés ont montré une efficacité certaine pour perturber la fluidité membranaire, plus ou moins prononcée selon la forme, Z ou E, la longueur de la chaîne alcoxy ou encore la présence du motif PEG. Les dérivés malonitrile quant à eux se voient diminuer leur effet photothermique au sein des bicouches lipidiques, après plusieurs cycles d’irradiation. L’ensemble de cette étude est une preuve de concept quant au potentiel des réponses photoinduites des analogues de la cyclocurcumine pour la perturbation de la fluidité membranaire vers une potentielle utilisation in vivoBeyond photodynamic therapy (PDT), there are several light-assisted therapeutic alternatives, including photothermal therapy (PTT) and photoisomerization, whose mechanical action would induce cellular damage within the membranes. Also, molecules able to simultaneously absorb two photons would overcome the need for high energy excitation per photon while maintaining sufficient tissue penetration. In this context, we were interested in designing and studying biomimetic analogues of cyclocurcumin (CC), a natural E/Z photoswitch. Guided by molecular modeling, those novel donor-acceptor compounds were structurally designed to increase the effective two-photon absorption cross section (σ2).First, we synthesized two classes of CC analogues bearing acceptor (oxo and malonitrile) and donor (hydroxy, alkoxy and amine) groups as well as a PEG arm to increase their hydrophilicity. Free in solution, the oxo derivatives show a reversible photoinduced isomerization, without any thermal isomerization in the dark, whereas the malonitrile derivatives do not photoswitch but undergo a vibrational relaxation. This is leading to a temperature increase, of interest in photothermal therapy. Finally, confined in a lipidic environment (liposomes bilayers and Langmuir monolayers), the direct E→Z isomerization kinetics of oxo compounds is strongly slowed down and no Z→E back isomerization is observed. Those compounds also showed a certain efficiency to disrupt membrane fluidity, more or less pronounced depending on the form, Z or E, the length of the alkoxy chain or the presence of the PEG unit. The malonitrile derivatives exhibit a diminished photothermal effect in lipid bilayers after several irradiation cycles.Taken together, this study is a proof of concept for the potential of photoinduced responses of cyclocurcumin analogs for disruption of membrane fluidity towards potential use in vivo
3
Schmitt, Bonell. "Curcumin analogues as ligands for Re (I) and (V)." Thesis, Nelson Mandela Metropolitan University, 2012. http://hdl.handle.net/10948/d1020975.
Анотація:
Coordination properties of 4-bromo-N-(diethylcarbamothioyl)benzamide (Hbeb) and 4-bromo-N-(diphenylcarbamothioyl)benzamide (Hbpb) with oxorhenium(V) and rhenium(I) are reported and discussed. Transition metal complexes of these ligands were studied due to the wide range of applications of thiourea derivatives in biological fields. N-[Di(alkyl/aryl)carbamothioyl]benzamide derivatives readily coordinate to metal ions as O,S-donors and the catalytic property of the complexes can be altered by these ligands, due to steric and electronic properties provided by various substituents. The coordination possibilities of curcumin with rhenium(V) are discussed, as well as the difficulties encountered. Analogues of curcumin have been made, which also contains a seven-spacer unit between the phenyl rings, which would be more reactive and more effective in bonding to rhenium and which have greater or a similar biological activity to curcumin. This was done by assessing the coordination properties of 1,5-bis(salicylidene)thiocarbohydrazide (H4salt) and 2,4-bis(vanilidene)thiocarbohydrazide (H4vant) with oxorhenium(V) and rhenium(I) starting materials. Two rhenium(V) complex salts of the core [ReX(PPh3)2]4+ (X = Br, I), containing a coordinated imido nitrogen, are reported. One is a ‘2+1’ complex, coordinating bi- and monodentately, with the other a similar ‘3+0’ complex containing a tridentate imido-coordinated Schiff base. Selected compounds were tested against oesophageal cancer cell lines in order to evaluate and compare their effectiveness in eliminating or reducing the cancer cells in the test medium during biological testing.
4
Souza, Nayane de. "Efeitos citotóxicos do DM-1 em células de melanoma resistentes a um inibidor de BRAF e na expressão de metaloproteinases." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/9/9143/tde-06122017-105135/.
Анотація:
Melanoma é o câncer mais agressivo e a mutação BRAF V600E é a mais frequente entre os pacientes. O vemurafenibe foi o primeiro inibidor específico desta mutação aprovado pela Food and Drug Administration. Entretanto, após cerca de seis meses há recidiva e superar os mecanismos de resistência responsáveis por este fenômeno ainda é um desafio. A curcumina é um tumérico com características antitumorais e anti-inflamatórias, entretanto sua baixa biodisponibilidade e estabilidade limitam seu uso e por isso impulsionaram a busca por análogos capazes de serem eficientes e comercializados. O DM-1, é um análogo monocetônico que apresentou efeitos antiumorais in vitro e in vivo em estudos anteriores. O objetivo deste trabalho foi avaliar os efeitos citotóxicos do DM-1 em células de melanoma sensíveis (naive) e resistentes ao vemurafenibe, bem como na modulação de metaloproteinases. As células de melanoma foram tratadas com diferentes concentrações de DM-1, e este composto foi citotóxico para linhagens sensíveis e resistentes ao vemurafenibe, além de induzir parada de ciclo celular em G1/G0 e diminuir o número de colônias, entretanto ele não foi seletivo em ensaios de citotoxicidade realizados com melanócitos e fibroblastos. O tratamento dessas células em doses subtóxicas resultou na modulação de metaloproteinases importantes no processo de invasão celular. O DM-1 reduziu as concentrações das metaloproteinases -1, -2 e -9 (MMP-1, -2 e -9) em um ensaio de quantificação de MMPs e a atividade das MMP-2 e -9 em um ensaio de zimografia de maneira célula dependente. As modulações negativas do inibidor de MMP TIMP-2 e MMP-14 para SKMEL-28 naive foram associadas a diminuição das atividades de MMP-2 e -9, enquanto que as modulações positivas para SKMEL-19 naive foram relacionadas ao aumento de MMP-2. Este composto ainda inibiu a migração das células e a formação de tubos por células endoteliais.Malignant melanoma is the most aggressive cancer and the BRAF V600E mutation is the most frequent among patients. Vemurafenib was the first specific inhibitor for this mutation approved by Food and Drug Administration. Therefore around six months later there is relapse and overcoming it is still a challenge. Curcumin is a turmeric and it has been deeply researched because of its anti-inflammatory and antitumoral effects. However the low stability limits its use, therefore, encouraged the investigation of analogues capable to be efficient and commercialized. DM-1 is a monoketone curcumin analog and it showed antitumoral effects in vitro and in vivo in previous studies The aim of this project was to evaluate the cytotoxical effects of DM-1 for vemurafenib responsive (naïve) and resistant melanoma cells, as well as metalloproteinases modulation. Melanoma cells were treated with different DM-1 concentrations, and this compound was cytotoxic for responsive and resistant cell lines, besides inducing G1/G0 cell cycle arrest and reducing the number of colonies, nonetheless it was not selective in assays performed with melanocytes and fibroblasts. Subtoxic treatment of those cells modulated important MMPs in the cell invasion process. DM-1 reduced metalloproteinases -1, -2 and -9 (MMP-1,-2 and -9) in a quantification assay, and MMP-2 and -9 activities by zymography in a cell-dependent way. Negative modulations of MMP inhibitor TIMP-2 and MMP-14 for SKMEL-28 naïve were associated with MMP-2 and -9 reduced activities, whereas positive modulations for SKMEL-19 naïve were correlated to MMP-2 increase. Furthermore, this compound reduced migration of those cells and endothelial cell tube formation.
5
Al-shdifat, Laith Mohammad Hilal. "Approaches to Enhancing the Properties of a Promising Curcumin Analogue." Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/25786.
Анотація:
A range of derivatives has previously been synthesized in order to overcome the stability and pharmacokinetic hurdles that hinder the in vivo investigation of the natural product, curcumin. One such derivative, pyrazole 15, has been demonstrated to inhibit the proliferation of a highly metastatic androgen-independent prostate cancer cell line (PC3).
In this work, pyrazole analogues, 15 and 32 and the corresponding curcumin analogues, 30 and 31 were synthesized using a microwave-assisted technique. A stability study, and in silico assessment, of curcumin 1 and thirteen pyrazole analogues (15,17, and 32-42) was hindered by the poor solubility of these analogues, as a result of their hydrophobicities. An attempt to improve the solubility of pyrazole 15, through host-guest complexation with three macromolecules, γ-cyclodextrin (γ-CD) 46, p-sulfonatocalix[4]arene sCX[4] 48 and cucurbit[7]uril CB[7] 52, was unsuccessful, presumably due to the lack of sufficient bonding interactions or the incompatibility of the pyrazole with the hydrophobic cavities in these molecules.
Eight polymeric micelle (PM) formulations were then fabricated with the aim of generating sufficient hydrophobicity to entrap pyrazole 15; seven formulations of the Pluronic® F127 72 based PMs, via the thin film hydration method, and one formulation incorporating POEGA-b-PS polymer based PMs (POEGA-b-PS-PMs 100), via the dialysis method.
All the empty PMs were shown to be stable, with particle sizes below 52 nm and polydispersity indexes (PDI) below 0.34, indicating homogeneity and stability. F127-PMs 93 were not able to accommodate pyrazole 15 (size 253.7 ± 25.4, PDI 0.63 ± 0.13, and lowest %DL 0.29 ± 0.01). Increasing the hydrophobicity of Pluronic® F127 72 by adding TPGS 73 in different ratios, as in the mixed micelles FT41-PMs 94, FT21-PMs 95, FT32-PMs 96 and FT11-PMs 97, resulted in better stability, a higher degree of monodispersity and the encapsulation of the hydrophobic pyrazole 15 (particle sizes 30 – 55 nm, PDIs 0.15 - 0.25, and %DL 1.08 - 1.19). The addition of the targeting moiety [D-Lys6]-LHRH 75, to give the FLHRH-PMs 98, helped improve the adaptability for the drug (particle size 57.6 ± 13.7 nm, PDI 0.41 ± 0.17 and %DL 0.48 ± 0.01), but not to the same levels as the addition of the hydrophobic TPGS 73.
Targeted mixed micelles FLHRHT32-PMs 99, reduced the particle size and the PDI, in comparison to targeted FLHRH-PMs 98 (without TPGS 73), as a result of increasing the hydrophobicity increases the stability (particle size 22.0 ± 0.2 nm, PDI 0.28 ± 0.03, and %DL 0.64 ± 0.05). POEGA-b-PS-PMs 100 displayed good stability in comparison to the Pluronic® F127 72 based PMs (particle size of 54.0 ± 0.3 nm and PDI 0.15 ± 0.01).
Finally, the resazurin reduction assay and IncuCyte® imaging technique were used to evaluate the biological activity (% cell viability) of pyrazole 15 and four promising formulations in three types of cancer cell lines; (PC-3), (MDA-MB-231) and (MCF-7). The experimental GI50 values for pyrazole 15 using 1% DMSO as a co-solvent were 2.5 ± 0.58 µM in PC-3, 1.26 ± 0.22 µM in MDA-MB-231, and 4.39 ± 0.63 µM in MCF-7.
Treatment with FLHRH-PMs 98 containing pyrazole 15 resulted in significant growth inhibition in comparison to the corresponding void in all three tested cell lines, while POEGA-b-PS-PMs 100 showed the same trend but did not produce any significant effect on MCF-7 cells. Treatment with TPGS-containing PMs (FT32-PMs 96 and FLHRHT32-PMs 99), resulted in growth inhibition, both in the presence and absence of pyrazole 15. These results suggest that these formulations can help improve pyrazole 15 solubility and thus enable further biological evaluation.
6
Abdelhamid, Dalia. "Natural Products as Lead Compounds for Drug Development. Part I: Synthesis and Biological Activity of a Structurally Diverse Library of Curcumin Analogues. Part II: Synthesis of Novel Sterol Natural Products and Related Analogues as Antileishmanial Ag." The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1299685922.
7
Tedesco, Serena. "Activation phenotypes of human monocyte-derived macrophages: methodological approaches and pharmacological modulation by curcumin analogues." Doctoral thesis, Università degli studi di Padova, 2016. http://hdl.handle.net/11577/3427229.
Анотація:
Under normal conditions macrophages provide immune surveillance and host defense in tissues to maintain homeostasis. However, upon sensing changes in the microenvironment, macrophages become activated, undergoing a morphological and functional switch. Activation of these cells is not an “all-or-none” process, but rather a continuum characterized by a wide spectrum of molecular and functional phenotypes ranging from the “classical” M1 activated phenotype, with a highly pro-inflammatory profile, to the “alternative” M2 phenotype, associated with a beneficial, less inflammatory, protective profile. The possibility to promote a macrophage protective phenotype has therefore become a therapeutic goal in the treatment of inflammatory conditions, and the identification of factors that control cell activation is currently an area of active research. Most studies in the field so far have been performed using primary mouse macrophages or macrophage cell lines, and a variety of monocyte differentiation protocols and macrophage activation markers are used by different labs. Moreover, the pharmacological control of human macrophage polarized activation has not been extensively explored. A number of natural and synthetic compounds, including chalcones and curcumin, the major active component isolated from the turmeric plant Curcuma longa, have been shown to induce effects on macrophage function (including antioxidant, anti-microbial, anti-carcinogenic and anti-inflammatory action) through multiple pharmacological mechanisms, including interference with TLR4 signaling. On these grounds, the specific aims of the present thesis were: a) to test cell models and differentiation protocols other than spontaneous blood-derived macrophage differentiation, namely the THP-1 cell line and CSF-1-driven differentiation, respectively; b) to profile the cytokine pattern into the culture medium, and c) to determine the modulation of phenotypic markers by pharmacological agents, namely curcumin derivatives known to suppress microglial activation through reduced production and release of pro-inflammatory mediators, as well as the underlying mechanisms of action.
Macrophages were differentiated from human PBMCs isolated by density gradient centrifugation, and cultured in RPMI 1640 medium with 10% FBS with CSF-1 for 6 days to obtain resting macrophages (M0). Classical (M1) and alternative (M2) phenotypes were generated using specific cytokines (0.1-1 μg/ml LPS or 20 ng/ml IL-4 plus 5 ng/ml IL-13, respectively) in the presence or absence of curcumin analogues or dexamethasone used a reference compound. Macrophage phenotypes were determined by flow cytometry using fluorocrome-labeled antibodies. Gene expression was analysed using qRT-PCR. The composition of macrophage conditioned media (MCM) was assessed with the Luminex technology. Curcumin analogues were kindly provided by Dr. Federica Belluti (University of Bologna).
When M2 polarization was induced with IL-4/IL-13 for 24h, we observed increased expression of M2 markers compared with M0. In terms of gene expression analysis of the CSF-1 driven macrophages, as expected, M1-polarized macrophages after 6 or 48 h showed higher mRNA levels of TNF-α and IL-1β compared with M0. The increase in mRNA was more marked after 48 h for all genes except TNF-α, which rose more sharply after 6 h. The anti-inflammatory cytokine IL-10 mRNA was unexpectedly more abundant in M1- than in M2-polarized macrophages, and peaked after 6 h. Compared with M0, M2 MCM showed higher levels of anti-inflammatory cytokines including CCL22 and IL-4. In contrast, M1 MCM was associated with higher levels of IL-1α, IL-1β, IL-6, IL-8, MCP-1, VEGF and TNF-α. Treatment with the curcumin analogue GG9 as well as CLI095, an inhibitor of TLR4 intracellular domain, reversed the LPS-induced up-regulation of CD80+ (M1) cells. A similar effect was maintained with the double positive CD80+/CCR2+ population. Unlike dexamethasone, which increased the percentage of CD163+ (M2) cells, the curcumin analogue GG9 did not affect M2 markers. Treatment with GG9 significantly blocked IL-1β cytokine production at the cell-bound level, in the protein lysate and in the medium. By contrast, curcumin and GG6 did not affect the levels of intra- and extracellular IL-1β. To investigate intracellular signaling pathways involved in cell activation, we performed Western blot analysis of factors involved in the NF-κB pathway. Activation with LPS significantly decreased the relative expression of IκB-α. By contrast, curcumin and GG6 were able to restore IκB-α amounts as did CLI095, whereas no effect was induced by GG9 treatment.
Therefore, M1 and M2 macrophages showed specific profiles of gene expression and surface markers, which were modulated by pharmacological treatment with dexamethasone or a curcumin analogue. Overall, these data suggest that polarized activation protocols may have an impact on the functional status of macrophages and are critical to further investigate pharmacological macrophage targeting.In condizioni normali i macrofagi sono i responsabili della risposta immunitaria e della difesa dell’ospite per mantenere l’omeostasi tissutale. In seguito a stimoli presenti nel microambiente, i macrofagi possono attivarsi, andando incontro a uno switch morfologico e funzionale. L’attivazione di queste cellule non è un processo “tutto o nulla” ma piuttosto un continuum caratterizzato da un ampio spettro di fenotipi molecolari e funzionali, i cui estremi sono rappresentati dal fenotipo definito “classico” o M1, con un profilo pro-infiammatorio, e da quello “alternativo” o M2, anti-infiammatorio e protettivo. La possibilità di promuovere un fenotipo macrofagico protettivo sta diventando un obiettivo terapeutico nel trattamento delle condizioni infiammatorie e l’identificazione di fattori che regolano l’attivazione cellulare è attualmente un’area di ricerca molto attiva. La maggior parte degli studi in questo ambito sono stati condotti utilizzando culture primarie di macrofagi di topo o linee cellulari; inoltre, i vari laboratori usano protocolli diversi di isolamento/differenziamento dei monociti e marcatori diversi di attivazione. Inoltre, il controllo farmacologico dell’attivazione macrofagica non è ancora stato indagato sufficientemente. Una serie di composti naturali e sintetici, ad esempio il calcone e la curcumina, il principale componente attivo della Curcuma longa (pianta nota per effetti anti-ossidanti, anti-microbici, anti-tumorali e anti-infiammatori) hanno dimostrato un effetto sulla funzione dei macrofagi, agendo attraverso diversi meccanismi farmacologici, ad esempio interferendo con il signaling del TLR4. Sulla base di queste premesse, gli scopi specifici di questo lavoro di tesi erano: a) testare un modello cellulare e un protocollo di differenziamento diverso da quello spontaneo, in particolare la linea cellulare monocitaria THP-1 e il differenziamento in presenza di CSF-1; b) determinare il profilo delle citochine presenti nel terreno di coltura e c) determinare la modulazione dei marcatori dei fenotipi di attivazione da parte di agenti farmacologici, in particolare da derivati di sintesi della curcumina, noti per la loro capacità di modulare l’attivazione di cellule murine di microglia attraverso la riduzione della produzione e rilascio di mediatori pro-infiammatori. I macrofagi sono stati differenziati a partire dai linfo-monociti umani isolati tramite gradiente di densità e coltivati in terreno RPMI + 10% FBS con aggiunta di CSF-1 per 6 giorni, ottenendo così macrofagi in condizioni basali (M0). Il fenotipo classico (M1) e il fenotipo alternativo (M2) sono stati ottenuti incubando i macrofagi M0 rispettivamente con 0.1-1 μg/ml LPS e IL-4 20 ng/ml + IL-13 5 ng/ml, in presenza o assenza di analoghi della curcumina, desametazone o CLI095, un inibitore del dominio intracellulare del TLR4 (questi ultimi utilizzati come composti di riferimento). I fenotipi macrofagici sono stati determinati tramite citofluorimetria utilizzando specifici anticorpi legati a fluorofori. L’espressione genica è stata valutata tramite qRT-PCR. La composizione dei terreni condizionati (macrophage conditioned media, MCM) è stata valutata con la tecnologia Luminex. Gli analoghi della curcumina sono stati gentilmente forniti dalla Prof.ssa Federica Belluti (Università di Bologna). In seguito a polarizzazione per 24 h con IL-4/IL-13 abbiamo osservato un aumento dell’espressione dei marcatori M2 rispetto a M0. Per quanto riguarda l’espressione genica di macrofagi differenziati con CSF-1, come atteso, i macrofagi M1 dopo 6 o 48h presentavano livelli superiori di mRNA per TNF-α e IL-1β rispetto a M0. L’aumento dell’mRNA era più marcato dopo 48 h per tutti i geni tranne TNF-α, che raggiungeva il picco a 6h. L’mRNA della citochina anti-infiammatoria IL-10 inaspettatamente era più espresso nei macrofagi M1 rispetto a M2 e raggiungeva il picco dopo 6 h. Rispetto a M0, l’MCM M2 era caratterizzato da alti livelli di citochine anti-infiammatorie tra le quali CCL22 e IL-4. Al contrario, l’MCM M1 presentava livelli elevati di IL-1α, IL-1β, IL-6, IL-8, MCP-1, VEGF e TNF-α. Il pre-trattamento con l’analogo della curcumina GG9 e il controllo positivo CLI095 ha prevenuto l’aumento indotto da LPS del marcatore M1 CD80. Un effetto simile è mantenuto anche sulla frazione di cellule a doppia marcatura CD80+/CCR2+. Al contrario del desametazone, che aumenta la percentuale di cellule CD163+ (M2), il GG9 non ha modulato i marcatori M2. Il trattamento con GG9 ha bloccato in maniera significativa la produzione di IL-1β valutata come citochina cell-bound, nel lisato cellulare o rilasciata nel terreno di coltura. Al contrario, l’analogo GG6 non ha modificato i livelli di IL-1β intra- ed extra-cellulare. Per indagare più nel dettaglio le vie di segnale coinvolte nell’attivazione di queste cellule, abbiamo effettuato analisi Western Blot di fattori coinvolti nella via di segnale di NF-κB. L’attivazione con LPS ha ridotto significativamente l’espressione relativa di IκB-α. Curcumina, GG6 e CLI095 hanno riportato IκB-α ai livelli di controllo, a differenza del GG9 che non modificava significativamente l’espressione di questa proteina. Pertanto, i macrofagi M1 ed M2 presentano specifici profili di attivazione genica e di marcatori di superficie che possono essere modulati in seguito a trattamento farmacologico con desametazone o analoghi della curcumina. Nel complesso, questi dati suggeriscono che protocolli di attivazione macrofagica possono avere un impatto sullo stato funzionale di queste cellule e sono fondamentali per definire nuove strategie di targeting farmacologico nei macrofagi umani.
8
SINGH, REETIKA. "COMPARATIVE ANALYSIS OF DIFFERENT CURCUMIN ANALOGUES TO INHIBIT TLR4 EXPRESSION IN BREAST CANCER- AN IN-SILICO STUDY." Thesis, DELHI TECHNOLOGICAL UNIVERSITY, 2021. http://dspace.dtu.ac.in:8080/jspui/handle/repository/18459.
Анотація:
Chronic inflammation is closely related to the emergence of a number of cancers,
including Breast cancer. Inflammation causes damage to the cell’s DNA which leads
to its abnormal growth and formation of tumor mass. One of the most commonly
known receptor responsible for inflammatory reactions is Toll-like receptor 4
(TLR4). It is activated majorly by bacterial LPS. Its activation further activates
Cyclooxygenase enzyme that catalyzes the conversion of arachidonic acid into
prostaglandins that lead to inflammation-like conditions. COX2 has also been
correlated to the promotion of tumor growth. It enhances metastasis, neoplasia,
lymphangiogenesis, etc., and is also related to poor prognosis in the breast cancer
patients. Curcumin derived from turmeric is a proven inhibitor of COX2. In my
project I have aimed to analyse and compare the inhibitory properties of other
analogues of curcumin that have previously been known to inhibit COX2. The
experimental layout began with screening the molecules on the basis of drug-likeness
using Lipinski rule of five. The suitable ligand molecules were further subjected to
other experiments, i.e., ligand docking and drug potential assessment. After all the
experiments, out of the five selected Curcumin analogues, Isoeugenol (extracted
from clove) was determined as the best fit molecule. The druglikeliness and drug
potential assessment results further validate its use as a potential inhibitor and can
further be tested for in-vivo efficacy. This drug can further be used in the 1st line
therapy of locally advanced and metastatic breast cancer patients as it will inhibit
COX2 that promotes metastasis of cancer cells. Isoeugenol extracted from Eugenia
caryophyllus (Cloves) can further be proven as a better COX2 inhibitor than its
chemical counterparts, as it is a natural compound and will therefore have
significantly less side effects.
9
"INVESTIGATING THE MASS SPECTROMETRIC BEHAVIOR OF NOVEL ANTINEOPLASTIC CURCUMIN ANALOGUES." Thesis, 2015. http://hdl.handle.net/10388/ETD-2015-01-1911.
Анотація:
Curcumin analogues are novel antineoplastic agents designed by structural modifications of the natural product curcumin to enhance its therapeutic effects. Various curcumin analogues displayed a significant cytotoxic effect towards different cancer cell lines including leukemia, melanoma, and colon cancer. In order to evaluate the safety, efficiency and metabolism of the new anticancer candidates, sensitive and high throughput analytical methods are needed. Thirteen curcumin analogues with the backbone structure of 3,5-bis(benzylidene)-4-piperidone were tested. The ionization behavior of curcumin analogues was investigated to reveal the possible mechanisms for the unusual formation of the positively charged [M-H]+ ions during single stage positive ion mode MALDI-MS analysis. Different ionization techniques (i.e., ESI, APCI, APPI, and MALDI) were used to evaluate this phenomenon. The results showed that curcumin analogues ionize into [M-H]+ along with the expected [M+H]+ species during MALDI and dopant free APPI-MS. In contrast, ESI, APCI and the dopant mediated APPI showed only the expected [M+H]+ peak. Our experiments revealed that photon energy triggers the ionization of the curcumin analogues even in the absence of any ionization enhancer such as matrix, solvent or dopant. Three proposed mechanisms for the formation of [M-H]+ were evaluated, two of them are probably involved in the [M-H]+ formation: (i) hydrogen transfer from the analyte radical cation and (ii) hydride abstraction.
In addition to the ionization behavior, the collision induced dissociation-tandem mass spectrometric (CID-MS/MS) fragmentation behavior of curcumin analogues was evaluated showing similar dissociation pathways that centered on the piperidone ring of the 3,5-bis(benzylidene)-4-piperidone moiety. The presence of different substitutes on that moiety resulted in specific product ions for each curcumin analogue. The fragmentation patterns were established to confirm the chemical structure of the tested compounds and identify the diagnostic product ions of each compound. Twelve common product ions were identified resulting from the breakage of various bonds within the piperidone moiety. There was a tendency for the formation of highly conjugated product ions that are stabilized via resonance. Common product ions were identified allowing for the establishment of a general MS/MS behavior for any curcumin analogue that belongs to the 3,5-bis(benzylidene)-4-piperidone structural family. The fragmentation routes and the genesis of the product ions were confirmed via MS3 and neutral loss analysis.
In summary, the ionization of curcumin analogues provided insights into the formation of unique [M-H]+ ions which were linked to photo ionization of such compounds without the need for additives, such as matrix, dopant or solvent. As such, curcumin analogues should be evaluated as MALDI matrices in the future. The CID-MS/MS analysis of curcumin analogues revealed a common fragmentation behavior of the tested compounds. It will be applied, in the future to determine metabolic by-products of the tested compounds as well as to develop targeted liquid chromatography (LC)-MS/MS methods.
10
Ze, Chen Chu, та 陳楚澤. "Xanthine Oxidase and α-Glucosidase Inhibition of Curcumin and Curcumin Analogs". Thesis, 2015. http://ndltd.ncl.edu.tw/handle/y83s8x.
Анотація:
碩士輔仁大學
食品科學系碩士班
103
Curcumin is a constituent from root and stem of family Zingiberaceae and Araceae. It has been used as a natural colorant in food industry. Curcumin has a great value in food and medicine, and it has been reported that curcumin could inhibit the activities of xanthine oxidase (XO) and α-glucosidase that make curcumin can be used for treatment of gout and diabetes. Chemical synthesis, which can change the structure of component, can enhance the activities, even create a new one. Therefore, the objective of this research is to evaluate the characterization of curcumin and its analogs as XO and α-glucosidase inhibitors. In this study, after screening XO and α-glucosidase inhibition, the components which have high inhibitory activities were calculated their half-maximal inhibitory concentration (IC50) and enzyme inhibitory kinetics. In order to calculating the inhibitory reaction constant, a docking algorithm simulates binding position between enzyme and inhibitors. The results showed that among all the curcumin and its analogs, CM-F had the strongest anti-oxidant activity with a half-maximal effective concentration (EC50) of 9.39 ± 0.16 μM, which was better than vitamin E (EC50=17.03 ± 0.09 μM). It also had a good XO inhibitory activity, and its IC50 value against XO was 6.14 ± 0.38 μM. The enzyme kinetic result showed it was competitive inhibition. As for α-glucosidase, CM-1 and CM-2 have good α-glucosidase inhibitory activities with the IC50 value of 21.06 ± 0.92 μM and 5.95 ± 0.09 μM, of which kinetic study indicates that both CM-1 and CM-2 are mix-competitive inhibitors on α-glucosidase. Furthermore, docking simulation showed there are 5 hydrogen bonds between XO and CM-F. However, only 1 and 2 hydrogen bonds involved in CM-1 and CM-2 binding to α-glucosidase, respectively. Accordingly, analogs of curcumin have the potentials using in the gout or diabetes patients.
Частини книг з теми "Curcumine – Analogues":
1
Awad, H., U. Das, J. Dimmock, and A. El-Aneed. "Tandem Mass Spectrometric Analysis of Novel Antineoplastic Curcumin Analogues." In Detection of Chemical, Biological, Radiological and Nuclear Agents for the Prevention of Terrorism, 223–31. Dordrecht: Springer Netherlands, 2014. http://dx.doi.org/10.1007/978-94-017-9238-7_15.
2
Ranjbar, Reza, Hossein Bagheri, Faezeh Ghasemi, Paul C. Guest, and Amirhossein Sahebkar. "Effects of Curcumin and Its Analogues on Infectious Diseases." In Studies on Biomarkers and New Targets in Aging Research in Iran, 75–101. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-56153-6_5.
3
Haldar, Animeshchandra G. M., Kanhaiya M. Dadure, and Debarshi Kar Mahapatra. "Recent Advancements of Curcumin Analogs and Curcumin Formulations in Context to Modern Pharmacotherapeutics Perspectives." In Applied Pharmaceutical Practice and Nutraceuticals, 121–45. First edition.: Apple Academic Press, 2021. http://dx.doi.org/10.1201/9781003054894-9.
4
Ginnebaugh, Kevin R., Aamir Ahmad, and Fazlul H. Sarkar. "Updates on the Promising Anticancer Activity of CDF, a Synthetic Curcumin Analogue." In Critical Dietary Factors in Cancer Chemoprevention, 3–12. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-21461-0_1.
5
Yang, Jennifer, and Gregory B. Lesinski. "Curcumin Analogs as Inhibitors of the Jak-STAT Signal Transduction Pathway." In Novel Apoptotic Regulators in Carcinogenesis, 247–66. Dordrecht: Springer Netherlands, 2012. http://dx.doi.org/10.1007/978-94-007-4917-7_10.
6
Wei, Dangheng, Yanghui Liu, Xiaoying Jia, Fengxia Guo, and Jiangzhang Wu. "A novel synthetic analogue of curcumin, B7, inhibits inflammatory factors expression in H2O2 induced endothelial cells." In IFMBE Proceedings, 636–38. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-29305-4_166.
7
Shioorkar, Mahesh G., and Omprakash S. Chavan. "ENVIRONMENTALLY BENIGN MICROWAVE ASSISTED CATALYST FREE SYNTHESIS OF CURCUMIN PYRIMIDINONE AND THIOPYRIMIDINONE ANALOGUES." In Futuristic Trends in Chemical, Material Sciences & Nano Technology Volume 2 Book 12, 197–207. Iterative International Publishers, Selfypage Developers Pvt Ltd, 2023. http://dx.doi.org/10.58532/v2bs12p2ch4.
Анотація:
Describe method consist of ecofriendly procedure for the preparation of Curcumin Pyrimidinone and Thiopyrimidinone analogues from Curcumin urea/thiourea With the help of MW irradiation for appropriate time. Green impact of reaction significantly enhanced due to no use of catalyst and under MWI process. Good to excellent yield of products, simple working strategy and easy purification are the advantage of present methodology
8
Sivalingam, Nageswaran, Thennavan Ulaganathan, Ganshyam Jayakumar, Siddarth Venkatt, Aadhavan Balakumar, and Sruthi Sritharan. "Unraveling the Chemistry of Curcumin for Colon Cancer Prevention and Treatment." In Multidisciplinary Applications of Natural Science for Drug Discovery and Integrative Medicine, 61–115. IGI Global, 2023. http://dx.doi.org/10.4018/978-1-6684-9463-9.ch003.
Анотація:
Colorectal cancer is the leading cause of mortality. Several studies are focused on understanding the molecular mechanism to develop potential therapeutics to enhance patient health standards. Curcumin is a bioactive component derived from Curcuma Longa implicated with a spectrum of anticancer properties such as antioxidants. It has been proposed to possess promising features in suppressing colon cancer proliferation. However, the pharmacokinetics studies denote that curcumin lacks bioavailability at the target site which leads to systemic metabolism and excretion. So, studies were diverted towards eliciting the importance of structural units and modifying curcumin conformation to improve the anti-cancer effect and bioavailability. Curcumin and its analogues were employed in clinical trials as a cotreatment group to alleviate the side effects of traditional chemotherapy. Here the authors review the recent trends in the usage of curcumin in colorectal cancer and emphasis relevant studies to update the current status of therapeutics.
9
Gokhale, Kunal M., Chaitanya Walekar, and Snehal Manje. "Novel Curcumin Analogues: Synthesis and Therapeutic Applications." In Current Overview on Pharmaceutical Science Vol. 5, 86–116. B P International (a part of SCIENCEDOMAIN International), 2023. http://dx.doi.org/10.9734/bpi/cops/v5/17813d.
10
Gupta, A. P., S. Khan, M. M. Manzoor, A. K. Yadav, G. Sharma, R. Anand, and S. Gupta. "Anticancer Curcumin: Natural Analogues and Structure-Activity Relationship." In Studies in Natural Products Chemistry, 355–401. Elsevier, 2017. http://dx.doi.org/10.1016/b978-0-444-63929-5.00010-3.
Тези доповідей конференцій з теми "Curcumine – Analogues":
1
Nagaraju, Ganji Purnachandra, Shijun Zhu, Roberto Diaz, Mamoru Shoji, and Bassel F. El-Rayes. "Abstract 3828: Potent curcumin analogues inhibit pancreatic cancer cell growth and angiogenesis." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-3828.
2
Leow, Pay Chin, Choon Pei Boon, Chong Yew Lee, Mei-Lin Go та Pui-Lai Rachel Ee. "Abstract 755: Design and synthesis of curcumin analogues as Wnt/β-catenin antagonists". У Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-755.
3
Kasinski, Andrea, Yuhong Du, Shala Thomas, Jing Zhao, Shi-Yong Sun, Fadlo Khuri, Chun-Yu Wang та ін. "Abstract B106: Inhibition of IKKb and NFκB signaling by a novel curcumin analogue". У Abstracts: Frontiers in Cancer Prevention Research 2008. American Association for Cancer Research, 2008. http://dx.doi.org/10.1158/1940-6207.prev-08-b106.
4
Mardiana, L., B. Ardiansah, A. Septiarti, R. Bakri, and G. Kosamagi. "Ultrasound-assisted synthesis of curcumin analogs promoted by activated chicken eggshells." In INTERNATIONAL SYMPOSIUM ON CURRENT PROGRESS IN MATHEMATICS AND SCIENCES 2016 (ISCPMS 2016): Proceedings of the 2nd International Symposium on Current Progress in Mathematics and Sciences 2016. Author(s), 2017. http://dx.doi.org/10.1063/1.4991200.
5
Pisano, Marina, Ilaria Sassu, Sara Cossu, Antonio Corrias, Valentina Nieddu, Mario Pescatori, Grazia Galleri, et al. "Abstract 3804: Molecular changes induced by the curcumin biphenyl analogue D6 in melanoma cells." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-3804.
6
Yadav, Babasaheb D., Sebastien Taurin, Lesley Larsen, and Rhonda J. Rosengren. "Abstract 3556: New curcumin analogues are cytotoxic towards estrogen receptor negative human breast cancer cell lines." In Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC. American Association for Cancer Research, 2010. http://dx.doi.org/10.1158/1538-7445.am10-3556.
7
Bao, Bin, Shadan Ali, Dejuan Kong, Sanila H. Sarkar, Zhiwei Wang, Sanjeev Banerjee, Amro Aboukameel, Subhash Padhye, Philip A. Philp, and Fazlul H. Sarkar. "Abstract 173: Targeted killing of cancer stem-like cells by a novel analogue of curcumin." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-173.
8
Pisano, Marina, Gabriella Pagnan, Maria Antonietta Dettori, Sara Cossu, Irene Caffa, Ilaria Sassu, Davide Fabbri, et al. "Abstract B202: A new curcumin analogue compound endowed with strong antitumor activity against neuroectoderma‐derived cancers." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 15-19, 2009; Boston, MA. American Association for Cancer Research, 2009. http://dx.doi.org/10.1158/1535-7163.targ-09-b202.
9
Amin, A. R. M. Ruhul, Michelle Lee, Mohammad A. Rahman, James R. Fuchs, Zhuo G. Chen, and Dong M. Shin. "Abstract 5425: Potent curcumin analogue FLLL-22, but not natural curcumin, targets the DNA damage pathway for apoptosis in lung and head and neck cancer cells." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-5425.
10
Obara, Megumi, Shinobu Ohnuma, Eduardo E. Chufan, Masaharu Ishida, Katsuyoshi Kudoh, Norihiko Sugisawa, Hideo Ohtsuka, et al. "Abstract 3242: Synthetic analogs of curcumin as modulators of multidrug resistance-linked ABC transporters." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-3242.