Modification Of Resveratrol And Antitumor Activity Of Its Derivatives

Resveratrol belongs to a molecular class of phytoalexins, which are defense compound and produced by higher plants in response to pathogenic attack or other stress conditions. Resveratrol has numerous biological activities, such as anticancer, antibacterial, antioxidation, heart protecting, antiestrogenic, antimutagenesis and so on.Resveratrol analogs and derivatives have similar pharmacological activity of resveratrol. Some of these compounds are superior to resveratrol in the activity and selectivity, and stability is often better than resveratrol'. Therefore, the resveratrol analogs and derivatives have become a research hotspot in recent years.In this paper, the natural extract of resveratrol as the raw material,15 derivatives of resveratrol compounds are synthesized. The structures are confirmed by 1H NMR, MS, IR and element analysis. Biological activities of synthetic compounds are investigated, and the relationship between the chemical structure and anti-tumor activity on the basis is discussed. The main content are as follows:Resveratrol as the raw material, keeping the stilbene backbone of resveratrol,15 kinds of derivatives of resveratrol are synthesized. Resveratrol has three hydroxyl groups which have a strong capacity for electronic, so resveratrol has a strong antioxidant activity. On this basis, DT-3, DT-6, DT-8, DT-12, DT-13, DT-15 are obtained by modifing the three hydroxyl groups of resveratrol. DT-1, DT-2, DT-4, DT-5, DT-7, DT-9, DT-10, DT-11, DT-14 are obtained by modifing one or two hydroxyl groups of resveratrol. The structure is confirmed by 1H NMR, MS, IR and element analysis.Anti-tumor activities of derivatives of resveratrol are tested by MTT method, and the structure-activity relationship is discussed. The compound DT-1 has the best anti-tumor activity than others of derivatives of resveratrol against the A549 cell line and its IC50 is 4.38 umol/L,which is 15 times higher resveratrol'IC50 which is66.2 umol/L and similar to adriamycin'IC50 which is2.36 umol/L;The compound DT-2 has the best anti-tumor activity against the LAC cell line and its IC50 is 5.55 umol/L, which is 4.5 times higher resveratrol'IC50 which is 24.9 umol/L; The compound DT-10 has the best anti-tumor activity against the Hela cell line and its IC50 is 1.41 umol/L. however resveratrol has little activity in Hela cell line.This experiment also has proved that the hydroxyl groups in resveratrol can enhance anti-tumor activity. The three hydroxyl groups of resveratrol show different biological activities and can be choosed to be modified. It has been found that derivatives of resveratrol with benzenesulfonyl substitute have good anti-tumor activity against the A549, LAC, Hela cell line and derivatives of resveratrol with benzene substitute are better than derivatives of resveratrol with straight-chain substitute in cell-growth inhibiton activitiy.