Docking study of some novel azole-oxime ether hybrids as potential antifungal agents

The incidence of infections caused by pathogenic fungi has increased significantly over the years. Nowadays, numerous antifungal drugs with various structures and scaffolds are known and available [1]. One of the most established antifungal azole drugs having rational versatility in structures is the miconazole family with the general structure of 1-(arylethyl)-1Himidazoles. On the other hand, oximes and oxime ether derivatives are a prominent structural motif found in numerous pharmaceutically active compounds. Many well-known drugs with various chemotherapeutic activities contain an oxime or oxime ether moiety in their structures [1].Recently, our research group has synthesized some novel azole-oxime ether hybrids (Fig. 1) and the products were examined for their in vitro antifungal activities against Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum [2]. Having realized the antifungal activities of these compounds, we were encouraged to investigate their possible interaction with the active site of cytochrome P450 14α-sterol demethylase which is a favorable target for most azole antifungal drugs. In this study, the binding properties and interaction of title compounds with Mycobacterium P450DM enzyme was investigated by molecular docking study. The interactions of several known antifungal drugs such as fluconazole, tebuconazole, albaconazole, and voriconazole with Mycobacterium P450DM enzyme were also investigated using molecular docking study. The Gipps-free energies (ΔG) for binding of aforementioned compounds with Mycobacterium P450DM enzyme have been indicated.