5º SEMINARIO QUÍMICA ORGÁNICA IQUIR 2026

SEMINARIO QUÍMICA ORGÁNICA 4-5-26

EXPOSITOR: Qco. Miguel R. Villarreal Parra

TÍTULO: "Quinazolin‐4(3H)‐One‐Based New Glitazones as Dual Inhibitors of α‐Glucosidase and Aldose Reductase: Comprehensive Approaches for Managing Diabetes Mellitus and Its Complications".

FUENTE: Tokalı, F.S., Demir, Y., Ateşoğlu, Ş., Tokalı, P. and Şenol, H. Archiv der Pharmazie, 2025, 358: e70033 https://doi.org/10.1002/ardp.70033.

DÍA, HORA y LUGAR: Lunes 4 de mayo de 2026, 14:00 h, Aula de graduados y virtual.

Modalidad virtual, Link: meet.google.com/wpi-ujuz-rok.

Resumen: A series of novel glitazones containing thiazolidine-2,4-dione and quinazolin-4(3H)-one moieties were synthesized to explore their potential as dual inhibitors of aldose reductase (ALR2) and α-glucosidase (α-Glu), two key enzymes involved in diabetes and its complications. In vitro assays revealed that compounds 8 (cyclohexyl substituted), 9 (phenethyl substituted), and 11 (phenyl substituted) exhibited potent inhibitory effects on both enzymes, with 11 being the most active, showing an ALR2 inhibition (Ki = 0.106 µM) approximately nine times more effective than the standard epalrestat (EPR) (Ki = 0.967 µM) and α-Glu inhibition (Ki = 0.648 µM) about six times stronger than acarbose (ACR) (Ki = 0.3.775 µM). Molecular docking and molecular dynamics simulations showed that compound 11 formed strong interactions with residues Trp-20, Gln-183, and Asp-43 for ALR2 and residues Arg-200, Arg-400, and Glu-271 for Phe-297. Cytotoxicity assays performed on healthy cell lines (HUVEC and BEAS-B2) revealed that the tested compounds were nontoxic at inhibitory concentrations. These findings highlight the potential of compound 11 as a promising dual inhibitor for managing diabetes and its complications, providing a foundation for further optimization and therapeutic exploration.