Synthesis and α-Amylase Inhibitory Potential and Molecular Docking Study of Nopinone-Based Thiazolylhydrazone Derivatives

A series of nopinone-based thiazolyhydrazone derivatives were synthesized by using nopinone derivated from natural beta-pinene as the starting material in three steps, including aldol reaction with aromatic aldehydes, condensation with aminothiourea, and cyclization with bromoacetophenone. The structures of synthesized compounds were characterized by H-1 NMR, C-13 NMR and HRMS. alpha-Amylase inhibitory activities of these compounds were also investigated. The results showed that 6 compounds among them had good inhibitory activities compared with the positive control acarbose. Especially, 4-(2-(2-(6,6-dimethyl-3-(4-methylbenzylidene))bicyclo[3.1.1]heptane-2-ylidene)indolyl-4-thiazol-4-yl)phenol (SZ14) exhibited remarkable alpha-amylase inhibitory activity with IC50 value of 4.11 mu mol/L. From the structure-activity relationship, the structure of R-2 gave great influence on the activities of thiazolyhydrazone derivatives. The kinetic inhibition study revealed that those 6 compounds were the noncompetitive inhibitor against alpha-amylase. It was used for molecular docking study to find out binding affinities for thiazolylhydrazone derivatives, and the binding mode of compound SZ14 with alpha-amylase was primarily investigated with molecular docking method.