DESIGN AND SYNTHESIS OF NOVEL 3,5-DIPHENYL PYRAZOLE DERIVATIVES AS SELECTIVE COX-2 INHIBITORS: ANTI-INFLAMMATORY, ANALGESIC AND ANTICANCER AGENTS

Abstract

A series of novel compounds (4a, 4b, 4c, and 4d) were designed, synthesized and characterized for their anticancer and anti-inflammatory activities. The anticancer efficacy was evaluated in vitro against MCF7 and ZR-75-1 human breast cancer cell lines, using parameters such as LC50, TGI, and GI50. Among the compounds, 4a and 4b exhibited the most potent anticancer activity, with compound 4a showing superior growth inhibition compared to the standard tamoxifen (TAM). The SAR analysis revealed that hydrophobic and electron-donating substituents on the scaffold enhanced anticancer efficacy, while bulky or hydrophilic substituents reduced potency. The compounds showed moderate anti-inflammatory action in rats, using the carrageenan-induced paw oedema model. Furthermore, the compounds were tested in a mammary tumorigenesis model, with 4b proving to be the most effective in delaying tumor formation and reducing tumor burden, similar to TAM. These findings suggest that the synthesized compounds hold promise as dual-action agents with both anticancer and anti-inflammatory potential. Further optimization and mechanistic studies are required to enhance their therapeutic efficacy and to explore their full potential as pharmaceutical candidates for cancer and inflammation.