The Computational Interaction Analyses of Some Vitamin D-Related Compounds with Sterol 14-Demethylase (CYP51) – Could It Be a Glimmer of Hope to Find New Anti-Mucormycotic Drugs Extracted from Plants-Derived Sterols?

Abstract

Introduction Many vitamin D analogs and sterols-related compounds have been identified and extracted from several plants including Solanaceae species. The aim of our study was to evaluate the antifungal potential of 15 vitamin D, D3 analogs, and some sterols-related compounds that have been detected in some plants along with 3 standard antifungal drugs, Isavuconazole, Fluconazole, and Voriconazole, on the Mucormycosis-sterol 14-alpha demethylase (CYP51) enzyme by in silico study. Methods In this work, the molecular simulation was used to prepare the specific enzyme and the antifungal profiles utilized for the molecular docking of the contemplated compounds and subsequent prediction for the mechanism of binding within the catalytic site of Sterol 14-Demethylase (CYP51) to speculate their binding affinities. Anti-fungal medications, Fluconazole and Voriconazole revealed drugs bound distant from the binding sites, but Isavuconazole bound close to the binding site. In this context, the 15 vitamin D and D3 compounds were somewhat seen in binding proximity, especially for Alfacalcidol, Eldecalcitol, and Inecalcitol. Results Seocalcitol and Isavuconazole had the lowest binding energies and were the closest ones connected to the binding cavities with the best binding free energies equal −13.21 ± 0.24 and −15.29 ± 0.25, respectively. Conclusion Isavuconazole and Seocalcitol could potentially be further assessed to be adjuvantly used as drugs to inhibit the fungal activity by targeting CYP51, a significant target for anti-fungal as well as anti-protozoan drugs, and hence could be efficient against mucormycosis.