Proposed Mechanism for the Antitrypanosomal Activity of Quercetin and Myricetin Isolated from Lam.: Phytochemistry, In Vitro Testing and Modeling Studies.

The in vitro activity of (promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells) and , from the fractions obtained from the hydroalcoholic extract of the aerial part of and the isolated compounds, has been evaluated. The chloroform, ethyl acetate and -butanol extracts showed significant antitrypanosomal activity towards , with IC values of 12.35, 13.53 and 12.93 µg/mL and with IC values of 14.94, 19.31 and 18.67 µg/mL, respectively. The phytochemical investigation of the fractions led to the isolation and identification of quercetin (), myricitrin (), biapigenin (), myricetin (), hyperoside (), myricetin-3--β-d-galactopyranoside () and myricetin-3'--β-d-glucopyranoside (). Myricetin-3'--β-d-glucopyranoside () has been isolated for the first time from this genus. The chemical structures were elucidated by using comprehensive one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic data, as well as high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). These compounds have also been evaluated for their antiprotozoal activity. Quercetin () and myricetin () showed noteworthy activity against , with IC and IC values of 7.52 and 5.71 µM, and 9.76 and 7.97 µM, respectively. The hexokinase (TbHK1) enzyme was further explored as a potential target of quercetin and myricetin, using molecular modeling studies. This proposed mechanism assists in the exploration of new candidates for novel antitrypanosomal drugs.