Design, synthesis and biological evaluation of novel 1,3-diarylpyrazoles as cyclooxygenase inhibitors, antiplatelet and anticancer agents

MedChemComm
2018.0

Abstract

With the aim of achieving new compounds possessing both anti-inflammatory and antiplatelet activities, we synthesized (<i>E</i>)-3-[3-(pyridin-3/4-yl)-1-(phenyl/sulfonylmethylphenyl)-1<i>H</i>-pyrazol-4-yl]acrylamides, and evaluated their COX-1 and COX-2 inhibitory and antiplatelet activities. Since COX-2 inhibitory and antiplatelet compounds have anticancer potential, we also screened their antiproliferative effects against three human cancer cell lines. Compounds <b>5n</b>, <b>5p</b>, <b>5s</b>, <b>10d</b>, <b>10g</b> and <b>10i</b> were determined as dual COX-2 inhibitor/antiplatelet compounds. Compound <b>10h</b> appeared to be a compound that exhibited antiplatelet activity without inhibiting the COX enzyme. Compounds <b>5h</b>, <b>10a</b> and <b>10i</b> were the most effective derivatives which displayed antiproliferative activity against Huh7, MCF7 and HCT116 cells. Particularly, compound <b>10i</b>, as the compound exhibiting the highest cytotoxic, antiplatelet and COX-2 inhibitory activity, was remarkable.

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