Microwave-assisted synthesis and biological evaluation of some arylidene derivatives of 3-Methyl-1-phenyl-1H-pyrazol-5(4H)-one with potential anti-cancer activity

Abstract

A series of 4-Arylidene-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one derivative was synthesized using microwave irradiation and characterized on the basis of spectral data. The anti-proliferative effect, drug suitability and their underlying molecular mechanism were investigated against a panel of normal and drug resistant cancer cell lines. Among the synthesized derivatives, compounds 5b, 5d, and 5i exhibited significant anti-proliferative effect whereas compound 5b emerged as the most potent anticancer agent. Tubulin polymerization analysis showed that compound 5b does not alter the tubulin dynamics in cancer cells. Compound 5b up-regulated mitochondria-dependent pro-apoptotic markers Bax, Caspase 3 and effectively induced apoptosis in multi-drug resistant cancer cell. The present study concludes that Compound 5b possess promising broad spectrum anticancer activity and its induction of apoptosis in cancer cells is mitochondria dependent.

Keywords

• 3-Methyl-1-phenyl-1H-pyrazol-5(4H)-one
• Arylidene
• Microwave irradiation
• Anti-cancer activity
• Cytotoxicity