In Vitro Antigiardial Activity and In Silico Target Exploration of Quassinoids Isolated from Castela tortuosa Liebm.

Giardiasis is a parasitic disease for which there is a growing need to develop new therapeutic alternatives due to the adverse effects associated with first-line treatments such as metronidazole and the increasing emergence of resistant strains. In this study, the in vitro antigiardial activity of three quassinoids, chaparrin (1), amarolide (2), and chaparrinone (3), isolated from the stems of Castela tortuosa Liebm., was evaluated. The compounds were obtained from the methanolic extract through fractionation and chromatographic purification, and their antigiardial activity was determined against Giardia lamblia trophozoites. In addition, in silico studies were conducted to evaluate their physicochemical, pharmacokinetic, and toxicological properties, as well as molecular docking studies against actin, aldose reductase (ARL), and pyruvate: ferredoxin oxidoreductase (PFOR). Chaparrinone (3) exhibited the highest antigiardial activity, with an IC50 18.98 μg mL−1, whereas chaparrin (1) and amarolide (3) showed lower activity. Amarolide (2) exhibited the highest binding affinities toward the molecular targets, while chaparrin (1) showed the most favorable overall toxicological/ADME profile. Taken together, these findings highlight chaparrinone (3) as a quassinoid of interest for the development of new antigiardial agents and support the need for further enzymatic, pharmacokinetic, and in vivo studies to more precisely determine its therapeutic potential.