Synthesis, Characterization, and Enzyme Inhibition Properties of 1,2,4-Triazole Bearing Azinane Analogues

Considering the importance of acetylcholine ester -ase (AChE, BchE) and alpha-glucosidase in the treatment of Alzheimer's disease and diabetes mellitus, the synthesis of novel azinane triazole-based derivatives as effective acetylcholinesterase (AchE), alpha-glucosidase, urease, lipoxygenase (LOX), and butyr-ylcholinesterase (BChE) inhibitors is described. Azinane analogue (2) was merged with 1,2,4-triazole to acquire 1-(4-toluenesulfonyl)-4-(3-mercap to-4-methyl-4H-1,2,4-triazol-5-yl) piperidine (8) through a list of intermediates including 1-(4-toluenesulfonyl)-4-(ethoxycarbonyl) piperidine (3), 1-(4-toluenesulfonyl)-4-(2-hydrazinocarbonyl)piperidine (5), and 1-(4-toluenesulfonyl)-4-[1-(methyl amino thiocarbonyl)-2-hydrazinocarbonyl]piperidine (7). The target molecules, 1-(4-toluenesulfonyl)-4-[3-(N-alkyl/ phenyl/aryl-2-ethanamoyl thio)-4-methyl-4H-1,2,4-triazol-5-yl] piperidine (12a-o), were achieved through the reaction of 8 with N-alkyl/phenyl/aryl-2-bromo ethanamides (11a-o) as electrophiles. These electrophiles were accomplished by a benign reaction of alkyl/phenyl/aryl amines (9a-o) and 2-bromo ethanoyl bromide (10). The spectral study of IR, 1D-NMR, and EI-MS corroborated the synthesized compounds. Methyl phenyl and methyl phenyl-substituted derivatives 12d and 12m with IC50 = 0.73 +/- 0.54; 36.74 +/- 1.24; 19.35 +/- 1.28; 0.017 +/- 0.53; and 0.038 +/- 0.50 mu M are found to be the most potent AChE, alpha-glucosidase, urease, and BChE inhibitors. The high inhibition potential of synthesized molecules against AChE, alpha-glucosidase, urease, and BChEenzymes inferred their role in enzyme inhibition properties.

Automated summary

This study describes the synthesis of novel azinane triazole-based derivatives as inhibitors for acetylcholinesterase, alpha-glucosidase, urease, and butyrylcholinesterase. The synthesized compounds showed high inhibition potential against these enzymes, indicating their role in enzyme inhibition properties.