Antibacterial azole derivatives: Antibacterial activity, cytotoxicity, and in silico mechanistic studies

• DOI: 10.1002/ddr.21721
• Publication Date: 2020-07-31T05:35:52Z
• Authors: Suat Sari; Ahmet Avci; Ebru Koçak; Didem Kart; Suna Sabuncuoğlu; İnci Selin Doğan; Zeynep Özdemir; İrem Bozbey; Arzu Karakurt; Selma Saraç; Sevim Dalkara
• Keywords: Azole; Broth microdilution; Docking (animal); Enterococcus faecalis

Abstract Azole antifungal drugs are commonly used in chemotherapy. Antibacterial effects of some topical antifungals, such as miconazole and econazole, have lately been revealed, which suggests a promising venue antimicrobial In this study, we tested an in‐house azole collection with properties for their antibacterial activity to identify dual‐acting hits using the broth microdilution method. The vitro screen yielded number potent derivatives against gram‐positive bacteria, Enterococcus faecalis Staphylococcus aureus. Compound 73 's minimum inhibitory concentration (MIC) value less than 1 μg/ml S. aureus ; however, none compounds showed noteworthy methicillin‐resistant (MRSA). All active were found safe at MIC values healthy fibroblast cells cytotoxicity test. Molecular docking studies most set programs flavohemoglobin (flavoHb) structure, proposed target antifungals activity, presented striking similarities regarding binding modes interactions between crystallographic data. addition being noncytotoxic, library was predicted be drug‐like free pan‐assay interference (PAINS). As result, current study revealed several potential both activities. Inhibition bacterial flavoHb suggested possible mechanism action title compounds.