Synthesis Of Resveratrol Analogues And Biological Evaluation Of Their Anti-tumor Activities

Resveratrol is a natural phenol compound, widely existed in human diets and medical plants, such as wine, blueberry, peanuts and Polygonum cuspidatum, etc. Resveratrol possess multiple biological functions, including anti-cancer, anti-diabetes, antioxidant, anti-ageing and cardiovascular protection. However, resveratrol has low water solubility and low bioavailability, it is readily metabolized and eliminated from the system, all of which limit its utilization as a drug candidate.Poly ethylene glycol (PEG) moieties are amphiphilic and soluble in most organic solvents as well as in water, they are generally low or non-toxic and can be eliminated by a combination of renal and hepatic pathways. PEGylated molecules often acquire better water solubility and lower LogP values.In order to improve the water solubility and ameliorate LogP values, and also to find compounds with better biological activity, six resveratrol analogues and eleven PEGylated-resveratrol analogues were designed and synthesized. The LogP values of these target compounds were determined by HPLC analysis, and the anti-tumor activities of these compounds were tested by MTT method on three tumor cell lines (MCF-7, DU-145 and Hela).Results reveal that by introducing small mPEG moieties to resveratrol and its analogues, their LogP values decreased relatively. According to the MTT assay, resveratrol only shows good anti-tumor activity in MCF-7 cell line, while compound 1b-1e only show moderate anti-tumor activity in DU-145 and Hela cell lines. However, none of the eleven PEGylated-resveratrol analogues show anti-tumor activity in three cancer cell lines.