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dc.contributor.authorDogan, Inci Selin
dc.contributor.authorSaraç, Selma
dc.contributor.authorSari, Suat
dc.contributor.authorKart, Didem
dc.contributor.authorEşsiz, Şebnem
dc.contributor.authorVural, Imran
dc.contributor.authorDalkara, Sevim
dc.date.accessioned2019-06-27T08:01:21Z
dc.date.available2019-06-27T08:01:21Z
dc.date.issued2017
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254
dc.identifier.urihttps://hdl.handle.net/20.500.12469/351
dc.identifier.urihttps://doi.org/10.1016/j.ejmech.2017.02.035
dc.description.abstractAzole antifungals are potent inhibitors of fungal lanosterol 14 alpha demethylase (CYP51) and have been used for eradication of systemic candidiasis clinically. Herein we report the design synthesis and biological evaluation of a series of 1-phenyl/1-(4-chlorophenyl)-2-(1H-imidazol-1-yl) ethanol esters. Many of these derivatives showed fungal growth inhibition at very low concentrations. Minimal inhibition concentration (MIC) value of 15 was 0.125 mu g/mL against Candida albicans. Additionally some of our compounds such as 19 (MIC: 0.25 mu g/mL) were potent against resistant C. glabrata a fungal strain less susceptible to some first-line antifungal drugs. We confirmed their antifungal efficacy by antibiofilm test and their safety against human monocytes by cytotoxicity assay. To rationalize their mechanism of action we performed computational analysis utilizing molecular docking and dynamics simulations on the C. albicans and C. glabrata CYP51 (CACYP51 and CGCYP51) homology models we built. Leu130 and T131 emerged as possible key residues for inhibition of CGCYP51 by 19. (C) 2017 Elsevier Masson SAS. All rights reserved.
dc.language.isoEnglish
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevier
dc.subjectAzoles
dc.subjectAntifungal
dc.subjectCandida species
dc.subjectCYP51
dc.subjectMolecular docking
dc.subjectMolecular dynamics simulation
dc.titleNew azole derivatives showing antimicrobial effects and their mechanism of antifungal activity by molecular modeling studies
dc.typeArticle
dc.identifier.startpage124
dc.identifier.endpage138
dc.relation.journalEuropean Journal of Medicinal Chemistry
dc.identifier.volume130
dc.identifier.wosWOS:000397180900010
dc.identifier.doi10.1016/j.ejmech.2017.02.035
dc.contributor.khasauthorEşsiz, Şebnem


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