Synthesis of Novel Curcumin Analogues and Their Evaluation as Selective Cyclooxygenase-1 (COX-1) Inhibitors

摘要: Curcumin, a major yellow pigment and active component of turmeric, has been shown to possess anti-inflammatory anti-cancer activities. Recent studies have indicated that cyclooxygenase-1 (COX-1) plays an important role in inflammation carcinogenesis. In order find more selective COX-1 inhibitors series novel curcumin derivatives was synthesized evaluated for their ability inhibit this enzyme using vitro inhibition assays COX-2 by measuring PGE2 production. All analogues showed higher rate inhibition. The most potent compounds were (1E,6E)-1,7-di-(2,3,4-trimethoxyphenyl)-1,6-heptadien-3,5-dione (4) (COX-1: IC50=0.06 μM, COX-2: IC50>100 selectivity index>1666) (1E,6E)-methyl 4-[7-(4-methoxycarbonyl)phenyl]-3,5-dioxo-1,6-heptadienyl]benzoate (6) IC50=0.05 index>2000). Curcumin therefore represent class highly promising candidates vivo studies.