Palabras clave
Trypanosoma cruzi
Esterol C-24-metiltransferasa
acoplamiento molecular
inhibidores
propiedades farmacocinéticas
Riboprine
Cómo citar
Resumen
Chagas disease, caused by Trypanosoma cruzi, remains a global health challenge due to the toxicity and low efficacy of current treatments. This study focused on identifying inhibitors of Sterol C-24-methyltransferase (Tc24SMT), an enzyme essential for ergoste-rol biosynthesis in the parasite and absent in humans, using computational approaches. A 3D model of Tc24SMT was obtained using AlphaFold (pLDDT >90), and two active sites (P1 and P2) were identified with DoGSiteScorer. A library of 104 S-adenosylmethionine analogues was filtered based on pharmacokinetic properties (SwissADME, ADMETlab) and Lipinski’s Rule, yielding 16 selected ligands. Molecular docking with AutoDock Vina revealed that Riboprine exhibited the highest affinity for P2 (-8.1 kcal/mol), with key interactions at residues such as Phe95 and Glu147. Zeatin riboside also showed promise (-7.7 kcal/mol) and a favorable safety profile. The results validate Tc24SMT as a therapeutic target and propose promising compounds for fu-ture in vitro studies. This work highlights the potential of computational tools in drug discovery for neglected diseases and emphasizes the need to integrate experimental validation and pharmaceutical optimization.
Citas
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