Computational investigation of the alkaloids of Pilocarpus microphyllus species as phytopharmaceuticals for the inhibition of sterol 14α-demethylase protease of Trypanosoma cruzi

Abstract

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:

• Chagas disease
• DFT
• molecular docking
• molecular dynamics
• ADMET predictions

Acknowledgments

We thank the institutional support from IFPI, UFPI, IFMA, UESPI, CENAPAD-UFC, FAPEPI and Sourcetech Chemistry LTDA. Special thanks to the Graduate Program in Chemistry of the Federal University of Piauí (PPGQ/UFPI) and the Computational Quantum Chemistry & Drug Planning Group (GQQC&PF/UESPI). The manuscript was written through the contributions of all authors. All authors have approved the final version of the manuscript.

Disclosure statement

There are no conflicts to declare.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.