Trypanosoma cruzi is a protozoan transmitted by the insect Triatoma infestans, popularly known as kissing bug. This protozoan causes the Chagas disease, a Neglected Tropical Disease. This study aimed to investigate, through DFT method and B3LYP hybrid functional, the physicochemical, pharmacokinetic, and pharmacodynamic properties of the alkaloids present in the leaves of the species Pilocarpus microphyllus (jaborandi) as a potential inhibitory activity on the protease sterol 14α-demethylase of T. cruzi associated with the techniques of molecular docking, molecular dynamics, MM-PBSA and ADMET predictions. The molecules of isopilosine, epiisopiloturine, epiisopilosine, and pilosine showed up the lowest binding energies by molecular docking, good human intestinal absorption, low penetration in the blood-brain barrier, antiprotozoal and anticarcinogenic activities in ADMET studies. It has been observed a better binding affinity of the sterol 14α-demethylase protease with isopilosine in molecular dynamics and MM-PBSA studies, which indicates it as a potential drug candidate for Chagas disease.Communicated by Ramaswamy H. Sarma.
Keywords: ADMET predictions; Chagas disease; DFT; molecular docking; molecular dynamics.