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

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.