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

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.

Constituents of buriti oil (Mauritia flexuosa L.) like inhibitors of the SARS-Coronavirus main peptidase: an investigation by docking and molecular dynamics.

Statistics show alarming numbers of infected and killed in the world, caused by the Covid-19 pandemic, which still doesn't have a specific treatment and effective in combating all efforts to seek treatments and medications against this disease. Natural products are of relevant interest in the search for new drugs. Thus, Buriti oil (Mauritia flexuosa L.) is a natural product extracted from the fruit of the palm and is quite common in the legal Amazon region, Brazil. In the present work, the anti-Covid-19 biological activity of some constituents of Buriti oil was investigated using in silico methods of Molecular Docking and Molecular Dynamics Simulations. The main results of Molecular Docking revealed favorable interaction energies in the formation of the 2GTB peptidase complex (main peptidase of SARS-CoV) with the 13-cis-ß-carotene ligands (ΔGbind = -10.23Kcal mol-1), 9-cis -ß-carotene (ΔGbind = -9.82Kcal mol-1), and α-carotene (ΔGbind = -8.34Kcal mol-1). Molecular Dynamics simulations demonstrated considerable interaction for these ligands with emphasis on α-carotene. Such theoretical results encourage and enable a direction for experimental studies in vitro and in vivo, essential in the development of new drugs with enzymatic inhibitory action for Covid-19.Communicated by Ramaswamy H. Sarma.