Synthesis, evaluation of cytotoxic properties of promising curcumin analogues and investigation of possible molecular mechanisms

Abstract

Curcumin is a popular, plant-derived compound that has been extensively investigated for diverse range of biological activities. Anti-cancer activity against various types of cancers and high safety profile associated with curcumin makes it very attractive. In this study, we report the synthesis and evaluation of pyrazole and click chemistry curcumin analogues for Head and Neck cancer. MTT assay against head and neck cancer cell lines CAL27 and UM-SCC-74A revealed the micromolar potency of the synthesized compounds. To determine the possible molecular mechanisms, effect of these analogues in the expression of pSTAT3, pFAK, pERK1/2 and pAKT was studied. Interestingly, compounds 2 and 5 significantly inhibited the pSTAT3 (Tyr 705) phosphorylation. As far as other compounds, they showed potent cytotoxicity against CAL27 however these compounds didn't show any activity on pSTAT3 phosphorylation at IC₅₀ concentration level. Molecular docking studies revealed the possible binding mode of pyrazole compound 2 in the SH2 domain of STAT3.

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Curcumin, a famous small molecule of natural product is being extensively explored for many biological activities. This study focuses on the synthesis and evaluation of pyrazole and click chemistry curcumin analogues for Head and Neck cancer activity. To determine the molecular mechanisms, a study was conducted to see the effect of the analogues in the expression of pSTAT3, pFAK, pERK1/2 and pAKT.

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