Piperonal-derived (E)-2-(2-(Benzo[d][1,3]dioxol-5-ylmethylene)hydrazineyl)-4-(aryl)thiazole derivatives as potential therapeutic leads for diabetes and Alzheimer's disease: In vitro and in silico evaluation against α-glucosidase, α-amylase, acetylcholinesterase, and butyrylcholinesterase

Abstract

A library of (E)-2-(2-(benzo[d][1,3]dioxol-5-ylmethylene)hydrazineyl)-4-(aryl)thiazole analogs were synthetic in a two-step reaction scheme and fully characterized by using various spectroscopic techniques. The synthetic compounds were explored for their potential therapeutic applications against validated drug targets of diabetes and Alzheimer's diseases. Thorough in vitro screening against α-glucosidase (AG), α-amylase (AA), acetylcholinesterase (AChE), and butylcholinesterase (BChE) resulted in profound inhibitory results by these compounds. Out of all active compounds, 17, 19, 18, 10, 13, and 14 were identified as potent inhibitors of AG compared to standard acarbose, as revealed by their enhanced inhibitory activity compared to standard. However, compounds 10, 17, 19, and 18 were recognized as more potent than acarbose against AA. In the case of AG and AA inhibition, compounds containing more electron-withdrawing nitro substitution showed remarkable inhibitory potential. In cases of AChE and BChE inhibitory activities, compounds 8–11, 5, and 6 were found to be potent inhibitors as compared to standard donepezil. Thorough kinetic studies were also carried out to see the inhibition mode of the compounds to complement the inhibitory studies. In silico studies were also performed to unravel the molecular interaction of the ligands (inhibitors) with the active site of each enzyme. The whole series was also evaluated for potential antioxidant activities via CUPRAC, FRAP, and DPPH methods and found to be significantly active compared to standard butylated hydroxytoluene (BHT). All complementary studies are well supported and identify a range of hit candidates for subsequent stages of drug development against diabetes and Alzheimer's disease.