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

• DOI: 10.1111/cbdd.13587
• Publication Date: 2019-07-01T15:49:16Z
• Authors: Suat Sari; Didem Kart; Suna Sabuncuoğlu; İnci Selin Doğan; Zeynep Özdemir; İrem Bozbey; Melis Gencel; Şebnem Eşsiz; Jóhannes Reynisson; Arzu Karakurt; Selma Saraç; Sevim Dalkara
• Keywords: Azole; Systemic candidiasis; Docking (animal)

Abstract Systemic Candida infections pose a serious public health problem with high morbidity and mortality. C. albicans is the major pathogen identified in candidiasis; however, non‐ spp. antifungal resistance are now more prevalent. Azoles first‐choice drugs for they ineffective certain caused by resistant strains. block ergosterol synthesis inhibiting fungal CYP 51, which leads to disruption of membrane permeability. In this study, we screened activity an in‐house azole library 65 compounds identify hit matter followed molecular modeling study their 51 inhibition mechanism. Antifungal susceptibility tests against standard including revealed derivatives 12 13 as highly active. Furthermore, showed potent antibiofilm well neglectable cytotoxicity mouse fibroblast assay. According docking studies, have necessary binding characteristics effective 51. Finally, dynamics simulations ( CACYP 51) homology model's catalytic site complexed were stable demonstrating excellent binding.