Synthesis And Antitumor Activity Evaluation Of Resveratrol Amide Derivatives

Resveratrol is a kind of phytoalexin and mainly found in grapes, knotweed, peanuts, mulberries and other plants. It had a wide range of pharmacological activities, such as antitumor, antioxidation, anti-inflammatory, antibacterial, antiviral, cardiovascular protection and so on. Among these activities, the study of antitumor activity of resveratrol was currently one of the hotspots. But resveratrol had the disadvantages of more targets, low bioavaiability and poor stability. So researchers are trying their best to find a novel of resveratrol derivatives of structural diversity, good selectivity, high activity and low toxicity.In this paper, we designed and synthesized two series of new resveratrol acrylamide and formamide derivatives, based on the structure of (E)-2,4-dimethoxy-6-(4-methoxystyryl)benzaldehyde. The selected synthetic routes were simple, the raw materials were easy to obtain and the yields of compounds were high. The structures of the synthetic compounds were comfirmed by1H NMR,13C NMR, MS and elemental analysis.The method of MTT was used to test the antiproliferative activities of resveratrol acrylamide derivatives against human breast cancer cells MCF-7, lung adenocarcinoma cells A549and mouse melanoma cells B16-F10. The results showed that all compounds had good antiproliferative activities. Among these compounds, the antiproliferative activity of compound a3was best. The IC50values of compound a3were1.33,1.88and2.08μM, respectively. In addition, we also tested the antiproliferative activities of resveratrol formamide derivatives against human hepatoma cells Smmc7721and gastric carcinoma cells SGC7901. The results showed that these compounds had good antiproliferative activities, and the activities were stronger than the positive control5-Fu. Among all resveratrol formamide derivatives, the antiproliferative activity of compound d21was best. The IC50values of compound d21were7.68and6.16μM against the two cancer cells.We preliminary studied the structure-activity relationship of these compounds on the basis of the antiproliferative activities and provided some theory for searching better activity of lead compounds for future.