Keywords
Trypanosoma cruzi
Sterol C-24-methyltransferase
molecular docking
inhibitors
pharmacokinetic properties
Riboprine
How to Cite
Abstract
La enfermedad de Chagas, causada por Trypanosoma cruzi, representa un desafío global de salud debido a la toxicidad y baja eficacia de los tratamientos actuales. Este estudio se centró en identificar inhibidores de la Esterol C-24-metiltransferasa (Tc24SMT), una enzima esencial en la biosíntesis de ergosterol del parásito y ausente en humanos, mediante enfoques computacionales. Se recuperó un modelo 3D de Tc24SMT usando AlphaFold (pLDDT >90) y se identificaron dos sitios activos (P1 y P2) con DoGSiteScorer. Una biblioteca de 104 análogos de S-adenosilmetionina fue filtrada mediante propiedades farmacocinéticas (SwissADME, ADMETlab) y la Regla de Lipinski, seleccionando 16 ligandos. El docking molecular con AutoDock Vina reveló que el Riboprine mostró la mayor afinidad por P2 (-8.1 kcal/mol), con interacciones clave en residuos como Phe95 y Glu147. Zeatin riboside también destacó (-7.7 kcal/mol), con un perfil de seguridad favorable. Los resultados validan a Tc24SMT como blanco terapéutico y proponen compuestos prometedores para futuros estudios in vitro. Este trabajo subraya, además, el potencial de las herramientas computacionales en el descubrimiento de fármacos para enfermedades desatendidas, destacando la necesidad de integrar validación experimental y optimización farmacéutica.
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