In our efforts to discover novel multi-target agents having better antitumor activities than celecoxib, 21 new aryl-substituted pyrazole derivatives possessing cis-diphenylethylene scaffold were mostly synthesized by a one-pot approach to ethyl 1,4,5-triaryl-1H-pyrazole-3-carboxylates via an improved Claisen condensation - Knorr reaction sequence. The cytotoxic effects of these compounds against three human cancer cell lines HT-29, Hep-G2, MCF-7 as well as their inhibition of NO production were studied. Results showed that incorporation of the important pharmacophoric groups of two original molecules celecoxib and combretastatin A-4 in a single molecule plays an important role in determining a better biological activities of the new coxib-hybrided compounds.
Keywords: COX-2; celecoxib; combretastatin; cytotoxicity; hybrid compounds; multi-target agents; synthesis design.
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