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dc.contributor.authorSarı, Suat
dc.contributor.authorKart, Didem
dc.contributor.authorSabuncuoğlu, Suna
dc.contributor.authorDoğan, İnci Selin
dc.contributor.authorÖzdemir, Zeynep
dc.contributor.authorBozbey, İrem
dc.contributor.authorGencel, Melis
dc.contributor.authorReynisson, Johannes
dc.contributor.authorKarakurt, Arzu
dc.contributor.authorSaraç, Selma
dc.contributor.authorDalkara, Sevim
dc.date.accessioned2020-12-13T09:56:47Z
dc.date.available2020-12-13T09:56:47Z
dc.date.issued2019
dc.identifier.issn1747-0277
dc.identifier.issn1747-0285
dc.identifier.urihttps://doi.org/10.1111/cbdd.13587en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/3538
dc.description.abstractSystemic Candida infections pose a serious public health problem with high morbidity and mortality. C. albicans is the major pathogen identified in candidiasis; however, non-albicans Candida spp. with antifungal resistance are now more prevalent. Azoles are first-choice antifungal drugs for candidiasis; however, they are ineffective for certain infections caused by the resistant strains. Azoles block ergosterol synthesis by inhibiting fungal CYP51, which leads to disruption of fungal membrane permeability. In this study, we screened for antifungal activity of an in-house azole library of 65 compounds to identify hit matter followed by a molecular modeling study for their CYP51 inhibition mechanism. Antifungal susceptibility tests against standard Candida spp. including C. albicans revealed derivatives 12 and 13 as highly active. Furthermore, they showed potent antibiofilm activity as well as neglectable cytotoxicity in a mouse fibroblast assay. According to molecular docking studies, 12 and 13 have the necessary binding characteristics for effective inhibition of CYP51. Finally, molecular dynamics simulations of the C. albicans CYP51 (CACYP51) homology model's catalytic site complexed with 13 were stable demonstrating excellent binding.en_US
dc.description.sponsorshipTubitak Hacettepe Universityen_US
dc.language.isoEnglishen_US
dc.publisherWileyen_US
dc.subjectBiological screeningen_US
dc.subjectMolecular modelingen_US
dc.subjectStructure-based drug designen_US
dc.titleAntifungal screening and in silico mechanistic studies of an in-house azole libraryen_US
dc.typeArticleen_US
dc.identifier.startpage1944en_US
dc.identifier.endpage1955en_US
dc.relation.journalChemical Biology & Drug Designen_US
dc.identifier.issue5en_US
dc.identifier.volume94en_US
dc.identifier.wosWOS:000487625900001en_US
dc.identifier.doi10.1111/cbdd.13587en_US
dc.contributor.khasauthorGencel, Melisen_US
dc.contributor.khasauthorEşsiz, Şebnemen_US


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