Synthesis and evaluation of edaravone-1,3,4-oxadiazole derivatives as potential anti-cancer inhibitors

Abstract

Edaravone, a pyrazole-based compound, exhibits inherent antitumor activity. Furthermore, its combination with compounds like 1,3,4-oxadiazoles may have significant potential in pharmaceutical chemistry, due to their diverse biological activities—including antiviral, antibacterial, anti-inflammatory, and anticancer effects. In this study, we synthesized edaravone-1,3,4-oxadiazole derivatives through a multistep route starting from phenyl-hydrazine and ethyl acetoacetate, involving pyrazole formation, ether synthesis, hydrazinolysis, cyclization, and final amine coupling. All the synthesized derivatives were thoroughly characterized using NMR, LC-MS and IR to confirm their chemical structures and assess their purity and molecular integrity. Through an in silico approach we identified two of the derivatives exhibited inhibition activity comparable with that of Erlotinib, an approved drug for inhibiting Epidermal Growth Factor Receptor (EGFR) kinase. Further in vitro analysis with the two derivatives showed significant results, they exhibited cytotoxicity toward MDA-MB-231 cells at low concentrations with the IC₅₀ values of the two derivatives being 1 μM and 1.9 μM, and these results were compared with the approved Erlotinib drug. This in vitro analysis corroborated the in silico approach. These results suggest that edaravone-1,3,4-oxadiazole derivatives are promising candidates for EGFR-targeted anticancer therapies.