Considering the importance
of acetylcholine esterase (AChE, BchE)
and α-glucosidase in the treatment of Alzheimer’s disease
and diabetes mellitus, the synthesis of novel azinane triazole-based
derivatives as effective acetylcholinesterase (AchE), α-glucosidase,
urease, lipoxygenase (LOX), and butyrylcholinesterase (BChE) inhibitors
is described. Azinane analogue (
2
) was merged with 1,2,4-triazole
to acquire 1-(4-toluenesulfonyl)-4-(3-mercapto-4-methyl-4
H
-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-4
H
-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 IC
50
= 0.73 ± 0.54; 36.74 ±
1.24; 19.35 ± 1.28; 0.017 ± 0.53; and 0.038 ± 0.50
μM are found to be the most potent AChE, α-glucosidase,
urease, and BChE inhibitors. The high inhibition potential of synthesized
molecules against AChE, α-glucosidase, urease, and BChEenzymes
inferred their role in enzyme inhibition properties.