Identification of Phyto-Compounds from Ilex kudingcha as Inhibitors of Sterol-14α-Demethylase Protease: A Computational Approach Against Chagas Disease

Trypanosoma cruzi causes chagas disease, a life threating disease in non-endemic and endemic regions globally, the life cycle of T. cruzi strictly depends on endogenous synthesis of sterol via 14-α-demethylase pathway. The available drugs for chagas disease treatment are currently resistance and parade unwanted side effects. Herein, molecular docking, QSAR, molecular mechanics/generalized born surface area (MM/GBSA) estimation, ADME screening, and molecular dynamics (MD) simulation were performed using Schrodinger suite to identify 14-α-demethylase protease antagonist from Ilex kudingcha . Density function theory of the hit ligands was carried out using Spartan 14 to investigate the molecular reactivity of the lead molecules. Nine (9) hit molecules were predicted as 14-α-demethylase protease inhibitors with binding energy range of − 7.632 to − 9.559 kcal/mol which was comparable to the standard drug (benznidazole = − 6.969), two lead molecules were further subjected to MD simulation over 50 ns predicting that kulactone and gallocatechin form stable interactions with vital residues at the catalytic site of the protein. DFT analysis revealed that, the hit ligands have the ability to donate and accept proton donating and accepting hence, effective as solubility and inhibitory agent and the ADME screening revealed, all the hit ligands obey Lipinski rule of five presenting them as drug candidate. The observations from this study predict kulactone and gallocatechin as putative antagonist of 14-α-demethylase protease and should be experimentally verify as a lead compound for chagas disease therapy.