Development of thiazole-appended novel hydrazones as a new class of α-amylase inhibitors with anticancer assets: an <i>in silico</i> and <i>in vitro</i> approach.
Chahal S, Punia J, Rani P, Singh R, Mayank, Kumar P, Kataria R, Joshi G, Sindhu J.
Hyperamylasemia is reported to be associated with numerous chronic diseases, including diabetes and cancer. Considering this fact, we developed a series of thiazole-clubbed hydrazones. The derivatives were explored for their <i>in vitro</i> α-amylase inhibitory activity, which was further corroborated with their anticancer assets using a panel of cancer cells, including colon cancer (HCT-116), lung cancer (A549), and breast cancer (MDA-MB-231). To better understand pharmacokinetics, the synthetic derivatives were subjected to <i>in silico</i> ADMET prediction. The <i>in vitro</i> based biological investigation revealed that compared to the reference drug acarbose (IC<sub>50</sub> = 0.21 ± 0.008 μM), all the synthesized compounds (5a-5aa) exhibited <i>in vitro</i> α-amylase inhibitory response in the range of IC<sub>50</sub> values from 0.23 ± 0.003 to 0.5 ± 0.0 μM. Along with this, the proliferations of the HCT-116, A549 and MDA-MB-231 cells were inhibited when treated with the synthesized compounds. Notable cancer cell growth inhibition was observed for compounds 5e, 5f and 5y, which correlated with their α-amylase inhibition. Additionally, the kinetics investigation revealed that 5b, 5e, 5f and 5y exhibit uncompetitive inhibition. 5b was found to be the least cytotoxic and most potent α-amylase inhibitor and was further validated by absorption and fluorescence quenching technique.