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Synthesis and Molecular Docking of Curcumin-Derived Pyrazole-Thiazole Hybrids as Potent α-Glucosidase Inhibitors
Jehan Y Al-Humaidi1, Lamia A Albedair1, Deepika Maliwal2
1Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. BOX 84428, Riyadh, 11671, Saudi Arabia.
Abstract:
α-Glucosidase inhibitors are critical for diabetes management, with pyrazoles and thiazoles emerging as effective options. This research highlights curcumin-based pyrazole-thiazole hybrids as potential inhibitors, synthesizing derivatives and evaluating their inhibitory capabilities. The study involved the synthesis of novel compounds using hydrazonoyl halides, confirmed through elemental and spectral analyses. The synthesized derivatives exhibited significant α-glucosidase inhibition, with IC50 values ranging from 3.37±0.25 to 16.35±0.37 μM. Among them, compound 7e demonstrated the strongest inhibition at 3.37±0.25 μM, outperforming the standard drug acarbose (IC50=5.36±0.31 μM). In silico assessments and molecular docking using AutoDock Vina revealed strong interactions, particularly with compounds 7b, 7e, 7f, and 7g, indicating their potential as stable and effective inhibitors. The results suggest that the synthesized pyrazole-thiazole hybrids hold promise as novel therapeutic agents for diabetes, warranting further exploration of their substituent effects for optimized inhibitor design.
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