Synthesis, crystal structure, and <i>in vitro</i> evaluation of newer 2,4-thiazolidinedione hybrids as α-glucosidase inhibitors
收藏资源简介：
In our continued efforts to explore newer inhibitors for AG to treat T2DM, we report the design and synthesis of a new library of VD-TZD hybrids employing a flexible and efficient synthetic approach for structural modification. Physicochemical, SC-XRD, and spectral analyses were performed to characterize the synthesized compounds and evaluate their <i>in</i> <i>vitro</i> AG inhibitory activity. Compared to Acarbose, VD-TZD hybrids displayed good AGI activity. Compounds <b>6f</b> and <b>6g</b> exhibited the strongest inhibitory activities against AG with IC<sub>50</sub> values of 18.16 ± 0.41 and 19.59 ± 0.78 μM. Compounds <b>6f</b> and <b>6g</b> exhibited an improved binding affinity for AG (PDB ID: 5NN8), with docking scores of −7.50 and −7.46 kcal/mol, respectively. The carbonyl group of compounds <b>6f</b> and <b>6g</b> formed hydrogen bonds with the amino acid residues LEU677, LEU678, and ARG411. The cell cytotoxicity assay indicated that compound <b>6f</b> exhibited low cytotoxic activity against HEK-293 cell lines. The <i>in silico</i> ADMET profile of compound <b>6f</b> indicates satisfactory oral drug-likeness and the absence of toxic effects. In conclusion, compound <b>6f</b> could be considered a promising lead compound for further optimization in AGI development for the treatment of T2DM.
