In silico study for prediction of novel bioactivities of the endophytic fungal alkaloid, mycoleptodiscin B for human targets

Abstract

Mycoleptodiscin B is a natural product extracted from the endophytic fungus Mycoleptodiscus sp. found in Sri Lanka and Panama with experimentally unexplored activities for human targets. In this study, a computational methodology was applied to determine druggable targets of mycoleptodiscin B. According to the computational toxicity and pharmacokinetics assessment, mycoleptodiscin B was proven to be a suitable drug candidate. Druggable targets for this compound, aromatase, acidic plasma glycoprotein and androgen receptor, were predicted using reverse docking. A two-step validation of those targets was performed using conventional molecular docking and molecular dynamic (MD) simulations, resulting in aromatase being determined as the potential therapeutic target. Based on molecular mechanics/Generalized Born Surface Area (GBSA) free energies and ligand stability inside the active site cavity during its 120 ns MD run, it can be concluded that mycoleptodiscin B is a potent aromatase inhibitor and could be subjected to further in vitro and in vivo experiments in the drug development pipeline. Consequently, natural product chemists can quickly identify the hidden medicinal properties of their miracle compounds using the computational approach applied in this research.