Molecular modeling studies of coruscanone (A) core nucleus as potential antifungal agents.

Abstract Fungal diseases could be serious and, in some cases, life-threatening. Considering the limited availability of antifungal agents in use, and the emergence of multi drug resistance (MDR) in fungal infections, there is a pressing need for the development of novel broad spectrum antifungal drugs with better efficacy. Coruscanone A analogues, natural derivatives which target the fungal lanosterol enzyme, were docked against lanosterol 14 α-demethylase (CYP51A1) that converts lanosterol to 4,4-dimethylcholesta-8,14,24-trien-3β-ol in the ergosterol biosynthesis pathway in order to stabilize the plasma membrane of the fungal species, and hence can be targeted for an effective antifungal therapy. For this purpose, we have employed Glide docking, using MAESTRO to predict binding modes of these Coruscanone (A) analogs to the enzyme. Results showed that some of these compounds were potent inhibitors of this enzyme compared to fluconazole (the known ligand of the enzyme that was used as control in the study) as evidenced by their docking scores and binding interactions. In conclusion, these finding may be helpful in the design of new effective and potent antifungal inhibitors. Graphic abstract Unlabelled Image [ABSTRACT FROM AUTHOR]