Synthesis and Activity Evaluation of Novel Prenylated Flavonoids as Antiproliferative Agents

Twenty prenylated flavonoids 1-20 were synthesized by glycoside hydrolysis dehydrogenation selective O-methylation O-prenylation and Claisen rearrangement reaction from abundant and inexpensive natural flavonoids naringin hespiredin quercetin and myricetin. Among them 1-7, 10-15 and 17-20 are novel compounds the natural product 3,3 ',4 ',7-tetramethoxy-8-prenyl-5-hydroxy flavonoid(16) was synthesized in a high yield. Their antiprolirative activities were evaluated in vitro on a panel of three human cancer cell lines(HeLa, HCC1954 and SK-OV-3). The results show that most of the target compounds displayed moderate to potent antiprolirative activities against the three cancer cells with half maximal inhibitory concentration(IC50 ) values from 0.49 mu mol/L to 95.07 mu mol/L. Among them 3,3 ',4 ',7-trimethoxy1-5-hydroxy1-8-prenyl flavonoid(12) exhibited the strongest antiprolirative activity against the three cancer cells mentioned above with IC50 values of 0.91-7.08 mu mol/L. 3 ',7-Dimethoxy-5-O-prenyl flavone(6) and 3 ',4 ',7-trimethoxy-5-O-prenyl flavone(10) showed selective antiproliferative activity against HCC1954 cells with IC50 value of 0.49 and 5.32 mu mol/L respectively.