Design, synthesis, biological evaluation, and docking study of chromone-based phenylhydrazone and benzoylhydrazone derivatives as antidiabetic agents targeting α -glucosidase

To develop novel alpha-glucosidase inhibitors, a series of chromone-based phenylhydrazone and benzoylhydrazone derivatives were designed, synthesized, and evaluated their inhibitory effects on alpha-glucosidase. The target compounds were characterized using 1H NMR, 13C NMR, and high-resolution mass spectra. Some of the com- pounds showed a varying degree of alpha-glucosidase inhibitory activity with IC50 values ranging from 6.59 +/- 0.09 to 158.55 +/- 0.87 mu M. Among them, compound 5c (IC50=6.59 +/- 0.09 mu M) was the most potent inhibitor by comparison with positive control acarbose (IC50=685.11 +/- 7.46 mu M). Enzyme kinetic, fluorescence analysis, circular dichroism spectra, and molecular docking techniques were employed to explain the underlying mo- lecular mechanisms of 5c inhibition on alpha-glucosidase. In vivo sucrose-loading test showed that 5c could suppress the rise of blood glucose levels after loading sucrose in normal Kunming mice. The cytotoxicity assay indicated that 5c exhibited low cytotoxicity.

Automated summary

In order to develop novel alpha-glucosidase inhibitors, a series of chromone-based phenylhydrazone and benzoylhydrazone derivatives were designed, synthesized, and evaluated for their inhibitory effects on alpha-glucosidase. The compounds showed varying degrees of inhibitory activity, with compound 5c being the most potent inhibitor. Mechanistic studies were conducted to elucidate the inhibitory mechanism of compound 5c on alpha-glucosidase. In addition, in vivo tests showed that compound 5c could suppress the rise of blood glucose levels after sucrose loading in mice, and cytotoxicity assays indicated low cytotoxicity of compound 5c.