Design synthesis and biological evaluation of novel 13-diarylpyrazoles as cyclooxygenase inhibitors antiplatelet and anticancer agents

摘要

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