Synthesis And Biological Activity Of Diphenyl Ketene Compounds

Tumor is one of the diseases threating human life and health. Antioxidants and non enzyme glycation inhibitor (NEGI) play a role in the prevention and treatment of the tumor. A large number of studies have shown that the diphenyl ketene curcumin compounds have strong antioxidation and non enzymatic glycosylation and can inhibit the growth of many tumor cell lines.Furthermore, they can be used as anti-cancer agent and anti-mutagen because of thier little side-effect and wide anti-canner spectrum. However,the bioavailability of curcumin is low due to it’s poor water solubility and structural instability. So to synthesize the new diphenyl ketene curcumin analogues with high activity by structural modification is very significant.According to published literatures,the study selected the high activity diphenyl ketene compounds as a lead-compound for further structural modification and tested their biological activities.The study also synthesized a series of curcumin analogues with different substituent on the benzene ring, using chemical structural modification and synthesis method. The structures of all compounds were characterized by means of mass spectrum,13C and1H nuclear magnetism resonance spectrum,which are proved to be the target products.The test results of diphenyl ketene compounds non-enzymatic glycosylation inhibition and anti-oxidation show that the compounds bearing o-diphenoxyl (A2,B2, C2, D2and E2) has higher activity and is stronger about20times than curcumin. On the basis of Hydroxy diphenyl ketene analogueswith4-OH (A1, B1, C1, D1and E1), the introduction of methoxy and bromo,single methoxy or two bromo groups in the ortho position of the4-hydroxyl group make the activity increased, but two methoxy groups decreased the activity.The active order was as followB>A>C>D>E. Among this diphenyl ketene compounds, o-phenolic hydroxyl compounds (A2, B2, C2,D2and E2) have stronger DPPH-scavenging actitvty than others and the activity sequence was A> B> C> D> E.ABTS+-scavenging actitvty roughly follow this active order B>C>E>D>A.Comparing DPPH-scavenging actitvty and non enzymatic glycosylation, compounds with o-dihydroxy (A2, B2, C2, D2and E2) showed both good activity. Overall, the compounds with strong DPPH-scavenging actitvty is also good at non-enzymatic glycosylation,but not vice versa. So the production of free radicals may be only a small part of the complex non-enzymatic glycosylation process and inhibition mechanism of diphenyl ketene compounds to non-enzymatic glycosylation needs further study.According to the inhibition activity result of these synthesized compounds to human prostate cancer cell line PC-3,the20compounds all showed strong inhibition on PC-3,especially the inhibitory activity of compounds b2on human prostate cancer cell line PC-3is about161times than that of curcumin,so it is expected to find out potential anti-tumor drugs from the curcumin analogues.