In silico-based identification of some selected phytoconstituents in Ageratum conyzoides Leaves as potential inhibitors of crucial proteins of Blastomyces dermatitidis

Abstract

Background: Blastomyces dermatitidis poses health threats to humans due to the frequency of infections (blastomycosis) and the increasing resistance to existing standard antifungal drugs. Moreover, the use of experimental in vitro and in vivo approaches in search for potent drug candidates is costly and time-consuming. The aim of this study was to evaluate the pharmacological properties of some reported phytoconstituents of Ageratum conyzoides against key enzymes of B. dermatitidis using in silico approach. Methods: A total of 29 reported bioactive compounds previously isolated from the leaves of A. conyzoides were randomly selected by a literature survey and their 3D Structure Data File (SDF) structures were downloaded from PubChem database. Applying molecular docking and dynamics simulation techniques, the phytoconstituents (ligands) were docked with the binding ligand pocket of three simulated enzymes; Saccharomyces cerevisiae lanosterol 14-alpha demethylase, human squalene epoxidase, and thymidylate synthase from Pneumocystis carinii using AutoDock 4.0 software and the poses that showed lowest binding energies were visualized using LigPlot+. Results: The results obtained from the docking studies of the selected phytoconstituents in A. conyzoides leaves showed that 4 out of the 29 ligands (sitosterol, catechin, stigmasterol, and 5-benzamido-4-oxo-6-phenylhexanoic acid) interacted with and showed very good binding affinity toward the 3 crucial antifungal drug target receptors, and exhibited significant inhibition compared to the standard drugs. Conclusion: Therefore, sitosterol, catechin, stigmasterol, and 5-benzamido-4-oxo-6-phenylhexanoic acid from A. conyzoides leaves hold a promising potential to be explored for their antifungal activities.