Design And Synthesis And Biological Activities Of Tetrahydrocurcumin Derivatives

In the thesis, a variety of useful bioactivities (including antioxidative, anti-inflammatory, anti-cancer, cancer and cardiovascular diseases chemopreventive) of curcumin and tetrohydrocurcu-min and the mechanisms were reviewed. Advances in research on curcumin derivatives and analogues were also summarized in the paper.In the thesis, we took tetrahydrocurcumin as the precursor compound to design its Mannich base derivatives for improving bioavailability of the compound as the low bioavailability of curcumin.27 Tetrahydrocurcumin derivatives have been designed and synthesized via reduction, acylation, C-alkylation, hydrolysis and Mannich Reaction from curcumin in the thesis. All of them have not been reported in literatures and their structures were confirmed by ¹H-NMR, ¹³C-NMR and IR. The synthetic methods were simple to deal with and the total yield was high.The antioxidative effects of tetrahydrocurcumin and some its derivatives were evaluated. Most of the derivatives have good activities of inhibiting LPS-activated microglia release of NO and were higher than tetrahydrocurcumin, especially the activities ofâ…¦d andâ…¦j were significantly higher than that of tetrahydrocurcumin and curcumin. Most of tetrahydrocannabinol curcumin derivatives have significant antiradical activities of DPPH, especially the compounds (â…¥d andâ…¦d) with the Pyrrolidine methylene moiety.The effects of tetrahydrocurcumin and its derivatives inhibiting proliferation of HL-60 were evaluated. The result showed that some derivatives had strong activities of inhibiting HL-60 proliferation and notable higher than that of the precursor,â…¦m with benzyl piperazine methylene group had strong proliferation activity and its IC₅₀ was equal to that of curcumin.According to our results, tetrahydrocurcumin Mannich base derivatives show good antioxidative and anti-tumor activities. They are worthy of more detailed investigation.