Romanian Society of Pharmaceutical Sciences

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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

1.Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
2.Department of Pharmaceutical Chemistry, Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan
3.Department of Pharmacy, Kohat University of Science and Technology, Kohat, Pakistan

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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.