Antifungal screening and in silico mechanistic studies of an in-house azole library

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dc.authoridReynisson, Jóhannes/0000-0003-4174-9512
dc.authoridEssiz, Sebnem/0000-0002-5476-4722
dc.authoridBozbey Merde, İrem/0000-0002-9290-938X
dc.authoridOzdemir, Zenyep/0000-0003-4559-2305
dc.authoriddogan, inci selin/0000-0003-4949-1747
dc.authoridKarakurt, Arzu/0000-0003-2209-0871
dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authorwosidReynisson, Jóhannes/AAL-9886-2021
dc.authorwosidEssiz, Sebnem/JVZ-2123-2024
dc.authorwosidBozbey Merde, İrem/HCI-8239-2022
dc.authorwosidOzdemir, Zenyep/AAJ-6384-2020
dc.authorwosidKART, DIDEM/I-8446-2013
dc.authorwosiddogan, inci selin/AAR-4150-2020
dc.authorwosidKarakurt, Arzu/ABH-9340-2020
dc.contributor.authorSari, Suat
dc.contributor.authorKart, Didem
dc.contributor.authorSabuncuoglu, Suna
dc.contributor.authorDogan, Inci Selin
dc.contributor.authorOzdemir, Zeynep
dc.contributor.authorBozbey, Irem
dc.contributor.authorGencel, Melis
dc.date.accessioned2024-08-04T20:46:51Z
dc.date.available2024-08-04T20:46:51Z
dc.date.issued2019
dc.departmentİnönü Üniversitesien_US
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.sponsorshipHacettepe Universitesi [014 D09 301 001-703, TDK-2017-14965, TPT-2015-6794]; Turkiye Bilimsel ve Teknolojik Arastirma Kurumu [113S060, 114S862]en_US
dc.description.sponsorshipHacettepe Universitesi, Grant/Award Number: 014 D09 301 001-703, TDK-2017-14965 and TPT-2015-6794; Turkiye Bilimsel ve Teknolojik Arastirma Kurumu, Grant/Award Number: 113S060 and 114S862en_US
dc.identifier.doi10.1111/cbdd.13587
dc.identifier.endpage1955en_US
dc.identifier.issn1747-0277
dc.identifier.issn1747-0285
dc.identifier.issue5en_US
dc.identifier.pmid31260179en_US
dc.identifier.scopus2-s2.0-85073996529en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage1944en_US
dc.identifier.urihttps://doi.org/10.1111/cbdd.13587
dc.identifier.urihttps://hdl.handle.net/11616/98995
dc.identifier.volume94en_US
dc.identifier.wosWOS:000487625900001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofChemical Biology & Drug Designen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_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

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