p-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studies

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dc.authoridKarakurt, Arzu/0000-0003-2209-0871
dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authoridSalva, Emine/0000-0002-1159-5850
dc.authoridŞALVA, EMINE/0000-0002-1159-5850
dc.authoridBozbey Merde, İrem/0000-0002-9290-938X
dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authorwosidKarakurt, Arzu/ABH-9340-2020
dc.authorwosidSARI, SUAT/A-5249-2017
dc.authorwosidSalva, Emine/ABI-2766-2020
dc.authorwosidKART, DIDEM/I-8446-2013
dc.authorwosidŞALVA, EMINE/CAH-3062-2022
dc.authorwosidBozbey Merde, İrem/HCI-8239-2022
dc.authorwosidSARI, SUAT/JCD-8070-2023
dc.contributor.authorBozbey, Irem
dc.contributor.authorSari, Suat
dc.contributor.authorSalva, Emine
dc.contributor.authorKart, Didem
dc.contributor.authorKarakurt, Arzu
dc.date.accessioned2024-08-04T20:47:11Z
dc.date.available2024-08-04T20:47:11Z
dc.date.issued2020
dc.departmentİnönü Üniversitesien_US
dc.description.abstractBackground: Azole antifungals are among the first-line drugs clinically used for the treatment of systemic candidiasis, a deadly type of fungal infection that threatens mostly immune-compromised and hospitalized patients. Some azole derivatives were also reported to have antiproliferative effects on cancer cells. Objective: In this study, 1-(4-trifluoromethylphenyl)-2-(1H-imidazol-1-yl)ethanone (3), its oxime (4), and a series of its novel oxime ester derivatives (5a-v) were synthesized and tested for their in vitro antimicrobial activities against certain ATCC standard strains of Candida sp. fungi and bacteria. The compounds were also tested for their cytotoxic effects against mouse fibroblast and human neuroblastoma cell lines. Molecular modeling studies were performed to provide insights into their possible mechanisms for antifungal and antibacterial actions. Methods: The compounds were synthesized by the reaction of various oximes with acyl chlorides. Antimicrobial activity of the compounds was determined according to the broth microdilution method. For the determination of cytotoxic effect, we used MTS assay. Molecular docking and QM/MM studies were performed to predict the binding mechanisms of the active compounds in the catalytic site of C. albicans CYP51 (CACYP51) and S. aureus flavohemoglobin (SAFH), the latter of which was created via homology modeling. Results: 5d, 5l, and 5t showed moderate antifungal activity against C. albicans, while 3, 5c, and 5r showed significant antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa. Most of the compounds showed approximately 40-50% inhibition against the human neuroblastoma cells at 100 mu M. In this line, 3 was the most potent with an IC50 value of 82.18 mu M followed by 5a, 5o, and 5t. 3 and 5a were highly selective to the neuroblastoma cells. Molecular modelling results supported the hypothesis that our compounds were inhibitors of CAYP51 and SAFH. Conclusion: This study supports that oxime ester derivatives may be used for the development of new antimicrobial and cytotoxic agents.en_US
dc.description.sponsorshipInonu University Scientific Researches Unit [TDK-2017-803]en_US
dc.description.sponsorshipThis project was supported by a grant from Inonu University Scientific Researches Unit (TDK-2017-803).en_US
dc.identifier.doi10.2174/1570180816666181128112249
dc.identifier.endpage183en_US
dc.identifier.issn1570-1808
dc.identifier.issn1875-628X
dc.identifier.issue2en_US
dc.identifier.scopus2-s2.0-85079849351en_US
dc.identifier.scopusqualityQ3en_US
dc.identifier.startpage169en_US
dc.identifier.urihttps://doi.org/10.2174/1570180816666181128112249
dc.identifier.urihttps://hdl.handle.net/11616/99197
dc.identifier.volume17en_US
dc.identifier.wosWOS:000514283100007en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherBentham Science Publ Ltden_US
dc.relation.ispartofLetters in Drug Design & Discoveryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAntimicrobial activityen_US
dc.subjectazolesen_US
dc.subjectCYP51en_US
dc.subjectcytotoxic effectsen_US
dc.subjectmolecular modelingen_US
dc.subjectoxime esteren_US
dc.titlep-Trifluoroacetophenone Oxime Ester Derivatives: Synthesis, Antimicrobial and Cytotoxic Evaluation and Molecular Modeling Studiesen_US
dc.typeArticleen_US

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