Investigation of Aldose Reductase Inhibitory Potential by Theoretical and Computational Analysis of 2-((4-fluorobenzyl)thio)-6-(4-methoxyphenyl)Imidazo[2,1-b][1,3,4]Thiadiazol

Year 2025, Volume: 9 Issue: 2, 209 - 225

Efdal Çimen

https://doi.org/10.32571/ijct.1763650

Abstract

In this study, the structural and biological properties of 2-((4-fluorobenzyl)thio)-6-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole were investigated in detail using theoretical and computational methods. Within the scope of the calculations, the molecule’s natural bond orbital analysis, molecular electrostatic potential surface mapping, nonlinear optical properties, highest occupied molecular orbital and lowest unoccupied molecular orbital energy levels, optimized molecular geometry, and Mulliken atomic charge distribution were obtained in detail using the PBEPBE and B3LYP methods with the 6-31G(d,p) basis set. The biological activity of the molecule was investigated by molecular docking on the crystal structures of the aldose reductase enzymes 4ICC and 4IGS. Docking results revealed binding energies of -9.50 kcal/mol for 4ICC and -10.00 kcal/mol for 4IGS, demonstrating a strong inhibitory effect, particularly against the 4IGS structure. Absorption, Distribution, Metabolism, Excretion, and Toxicity analyses demonstrated that the molecule conforms to Lipinski's rules and has high oral bioavailability. The results suggest that FTMT is structurally stable, biologically active, and a potential therapeutic candidate, particularly for diabetes-related diseases.

Keywords

Natural bond orbital , nonlinear optical properties , molecular docking , mulliken atomic charge , molecular electrostatic potential surface mapping

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