Molecular modeling of a series of pyridinecarboxamidrazone-azole derivatives with antifungal activity

Abstract

Despite the large number of current antifungals used for treating fungal infections, the increased resistance of these microorganisms over the years has been one of the main and major challenges for medicine in the new century. Thus, it remains necessary to discover novel antifungal agents. The objective of this study was to identify the stereoelectronic features related to the antifungal activity of a series of triazoles and imidazoles derivates with activity against Candida albicans, also pharmacokinetic and toxicity in silico were evaluated to guide the rational design and identification of new antifungal agents. The results showed that features such as maintenance of imidazole ring, the profile of distribution and density of high occupied molecular orbital and conformational aspects in these derivatives were important for the activity and also demonstrate that all the compounds showed good oral bioavailability and low theoretical toxicity profile when compared to antifungals on the market, presenting a promising profile for future in vivo studies.