Substituted Benzylidene Cyclopentanone Ketone Derivatives Of The Design, Synthesis And Anticancer Activity

It was summarized the recent progresses of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment and chemoprevention of cancers in the thesis, and the potential mechanisms as well.Sixteen target compounds were designed and synthesized, basing on 2-(E)-(4-hydroxy-3-methoxybenzylidene)cyclopentanone as the lead compound, all of which are innovative and have not been reported yet. Encompassed are twelve 2-(E)-(4-cyclopentyloxy-3-methyloxybenzylidene)cyclopeantanone Mannich bases, two 2-(E)-(4-hydroxy-3-methoxybenzylidene)cyclopentanone carbonyl derivatives, one 2-(E)-(4-hydroxy-3-methoxybenzylidene)cyclopenta-none Mannich bases and one 2-(E)-(4-cyclopentyloxy-3-methyloxybenzylidene) cyclopentanone. All of them were characterized by means of IR, ¹HNMR, MS and elemental analysis. Antitumor activity screens in vitro showed that YL-03, YL-07, YL-08, YL-09, YL-10, YL-12, YL-13, YL-14 及 YL-16(IC₅₀: 0.98～10.18μM)exhibited good inhibition of BE1-7402 and KB, whereas inhibitive activity of YL-02((IC₅₀=1.91μM), YL-11(IC₅₀=7.18μM) to BE1-7402 and YL-06(IC₅₀=4.17) to KB are good. YL-01,YL-04, YL-05 and YL-15 are of little cytotoxic activity on two cell lines. Further pharmacological tests and mechanism researches are underway.