COMPUTATIONAL AND PHARMACOLOGICAL EVALUATION OF
HETEROCYCLIC 1,3,4-OXADIAZOLE AND PYRAZOLES NOVEL
DERIVATIVES FOR TOXICITY ASSESSMENT, TUMOUR INHIBITION,
ANTIOXIDANT, ANALGESIC AND ANTI-INFLAMMATORY ACTIONS
MUHAMMAD FAHEEM 1, ARIF-ULLAH KHAN 1*, HUMAIRA NADEEM 2, FAWAD ALI 1,3
1Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
2Department of Pharmaceutical Chemistry, Riphah Institute of Pharmaceutical Sciences, Riphah International University,
Islamabad, Pakistan
3Department of Pharmacy, Kohat University of Science and Technology, Kohat, Pakistan
*corresponding author: arif.ullah@riphah.edu.pk
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Abstract:
The present research work was focused on the computational and pharmacological potential of 1,3,4-oxadiazole and pyrazole
novel derivatives including: N-{4-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methoxy]phenyl acetamide (a3), 5-[(naphthalen-2-yloxy)
methyl]- 1,3,4-oxadiazole-2-thiol (b3), 3-phenyl-5-(o-hydroxyphenyl)-1-[2-(p-N-acetylaminophenoxyacetylpyrazole (a6) and 3-
phenyl-5-(o-hydroxy phenyl)-1-[2-(2’-naphthyloxy)acetyl] pyrazole (b6). Docking against targets including epidermal
growth factor receptor (EGFR), tubulin, cyclooxygenase-2 (COX-2) and 5-lypoxygenase (5-LOX) were followed by the
investigation of a3, b3, a6, and b6 for toxicity, tumour inhibition, free radical scavenging, analgesic and anti-inflammatory
potential. Compound a3 showed binding and moderate inhibitory effects in all assays, b3 possess good affinity for COX-2
and 5-LOX which can be correlated to its highest analgesic and anti-inflammatory effects. Compound a6 showed binding to
all targets and antioxidant potential, with an EC50 value of 100 μg/mL, b6 formed two hydrogen bonds with tubulin and was
the most potent in the toxicity assessment and tumour inhibition with LC50 values of 2.47 and 5.51 μg/mL respectively.

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