Synthesis characterization and evaluation of novel triazole based analogs as a acetylcholinesterase and α-glucosidase inhibitors

Abstract

A series of novel triazole analogs (10a-k) bearing piperidine were synthesized in an aprotic solvent on the most effective pharmacophore with acetylcholinesterase (AChE) and α-glucosidase inhibitory activity. Triazole analogs (10a-k) were obtained in excellent yields (75–90 %) and characterized by EI-MS, IR, 13C NMR and 1H NMR. The newly synthesized triazole analogs (10a-k) showed potent AChE inhibitory activity in the range of Ki = 0.0155 ± 1.25 µM to 0.557 ± 0.50 µM, IC50 = 0.031 ± 0.85 to 0.537 ± 0.76 µM than Eserine (0.04 ± 0.001 µM) having strong electron-withdrawing fluorine group on the pyridine ring was recorded as a most potent inhibitor of AChE while (%) inhibition against α-glucosidase was ranging between 52.36 ± 1.67 to 85.35 ± 1.39. The kinetic study predicted that triazole analogs (10a-k) followed the un-competitive and mixed type of inhibition against AChE. In silico molecular docking was performed at the active site of the AChE co-crystal structure (PDB ID:1NEN). The results of molecular docking corelate will with the experimental findings.

Keywords

• 1,2,4-triazole
• Piperidine
• Acetylcholinesterase inhibition
• α-glucosidase inhibition