Design And Synthesis And Biological Activities Of Novel Curcumin Derivatives

In this thesis, advances in research on curcumin and its derivatives and angalogues were reviewed. The bioactivities of anti-cancer, anti-oxidation, anti-inflammatory, treatment of cardiovascular diseases and their mechanisms were introduced in detail.Curcumin and tetrahydrocurcumin were taken as lead compounds. The curcuminoid pyrazole (HC) as the basic nucleus, the introduction of methyl amine in the benzene ring, two series of derivatives of HC Mannich bases were designed. A synthetic scheme was developed, and the first series target compounds were synthesized from curcumin, followed by pyrazole cyclization and Mannich reaction. The second series target compounds were synthesized from tetrahydrocurcumin, followed by acylation, C-alkylation, hydrolysis, Mannich reaction and pyrazole cyclization. All the 22 compounds have not been reported in literature. The structures of the target compounds were confirmed by 1H-NMR,13C-NMR and MS.The effects of curcumin, curcuminoid pyrazoland and its derivatives inhibiting proliferation of HL-60 were evaluated. The result showed that most of derivatives have strong activity of inhibiting HL-60 proliferation and ZL-HC-18 has the best activity. The effects of curcumin and 5 derivatives inhibiting proliferation of Du145 were evaluated. The result showed that all the 5 derivatives had sronger anti-tumor activity than curcumin, especially ZL-HC-06.According to our results, curcuminoid pyrazole Mannich base derivatives show good anti-tumor activity. They are worthy of more detailed investigation.