Design, synthesis, and molecular docking studies of benzimidazole‐1,3,4‐triazole hybrids as carbonic anhydrase I and II inhibitors
Abstract
In this study, with an aim to develop novel heterocyclic hybrids as potent enzyme
inhibitors, we synthesized a series of 10 novel 2- (4- (4- ethyl- 5- (2- (substitutedph
enyl)- 2- oxo- ethylthio)- 4H- 1,2,4- triazol- 3- yl)- phenyl)- 5,6- dimethyl- 1H- benzimid
azole (5a– 5j) derivatives and characterized by
1
H- NMR,
13
C- NMR, and HRMS.
These compounds were evaluated for their inhibitory activity against hCA I and
hCA II. All the compounds exhibited good hCA I and hCA II inhibitory activities
with IC
values in range of 1.288 μM– 3.122 μM. Among all these compounds,
compound 5e, with an IC
50
value of 1.288 μM is the most active against carbonic
hCA I. Compound 5h with an IC
50
value of 1.532 μM is the most active against
carbonic hCA- II. Compounds 5a– 5j were also evaluated for their cytotoxic effects
on the L929 mouse fibroblast (normal) cell line. The compounds were also analyzed
for
their antioxidant capacity
by
TAS, FRAP, and
DPPH activity. Enzyme
inhibition
kinetics showed all compounds 5a–
5j
to inhibit the enzyme by non-
competitive.
The most active compound 5e
for hCA I and compound 5h
for hCA
II
were subjected to molecular docking, which revealed their binding interactions
with
the enzyme's active site, confirming the experimental findings.
50