Abstract
A series of novel
N
′-arylmethylidene-3-methyl-1-phenyl-6-
p
-chlorophenyl-1
H
-pyrazolo[3,4-
b
]pyridine-4-carbohydrazide (
2a
–
2t
) has been synthesized from hydrazide (
1
). The structures of newly synthesized compounds were confirmed by FT-IR, EI-MS,
1
H NMR and
13
C NMR techniques. The title compounds were evaluated for antioxidant and antiplatelet aggregation effect induced by arachidonic acid (AA) and collagen. All the compounds have exhibited high antioxidant potential and antiplatelet activity but (
2c
,
2e
,
2f
,
2g
,
2i
,
2m
,
2o
and
2q
) have revealed superlative antiplatelet activity. The molecular docking against cyclooxygenase-1 and 2 (COX-1 and COX-2) and quantitative structure-activity relationship (QSAR) were performed in describing their antiplatelet potential against AA and collagen along with antioxidant potential determined by ABTS, DPPH and iron chelating methods. The molecular docking study exhibited that compounds (
2c
,
2e
,
2f
,
2g
,
2i
,
2l
,
2m
,
2o
and
2q
) were found to be active against COX-1 while
2o
compound also showed activity against COX-2. Compounds
2g
and
2l
were found to have higher energy stabilization values in comparison to Aspirin. Computational evaluations both molecular docking and QSAR are in good agreement with antiplatelet and antioxidant activities of the compounds (
2a
–
2t
). All the compounds especially
2g
,
2l
,
2m
might be promising antiplatelet agents and might be helpful in the synthesis of new drugs for the treatment of cardiovascular and anti-inflammatory diseases.
Graphical Abstract