Synthesis And Anticancer Activities Of Fluorinated Genistein Derivatives

Objective:Genistein is an isoflvaone, one kind of lesser distributed flavonoids in nature. These days, genistein attracts more and more attention with its remarkable effect on tumor. And genistein has shown antitumor activities in breast cancer, prostate cancer, colon cancer, and so on. However, the anticancer activity of genistein is low because it is not or little absorbed in intestines. In order to search for anticancer substances with high efficacy, low toxicity and minimum side effects. We are interested in the synthesis and anticancer effect of gem-difluoromethylenated genistein derivatives.Methods:Treatment of 4',5,7-trihydroxyisoflavone 1 with HCF2Cl gas in the presence of NaOH in dioxane/H2O gave 2 and 3. The reaction of 2 with RX in the presence of K2CO3 at reflux temperature gave 2a-2g. We tested their anticancer activities against leucocythemia (HL-60), colorectal adenocarcinoma (HT-29) and human gastric adenocarcinoma (SGC-7901) cells lines by MTT-Based Assay. And we also elucidated the general structure-activity relationship of those compounds .Results:We have synthesized a series of genistein derivatives, and the derivatives were tested for their in vitro anti-cancer activities against leucocythemia (HL-60), colorectal adenocarcinoma (HT-29) and human gastric adenocarcinoma (SGC-7901) cell lines by MTT-Based Assay. It appeared that these closely related molecules displayed remarkable differences in cytotoxicity. Conclusion:It indicated that 5,4′-di-n-octoxyl-7-gem-difluoromethylenegenistein 2f had the strongest and 5,4′-di-n-propoxy-7-gem-difluoromethylenegenistein 2c had the second strongest activities against HL-60, HT-29 and SGC-7901 tumor cells. General structure-activity relationship of those compounds were elucidated from these data.