Anti-breast cancer activity of heteroaryl chalcone derivatives

In an attempt to develop effective anticancer therapeutics, a new series of heteroaryl chalcone compounds were designed, synthesized, and examined for their antiproliferative effects on two breast cancer cell lines and one matching non-cancer breast cell line. The structure-activity relationship (SAR) analysis suggested that the compounds derived from thiophene chalcones (6-17) exhibited generally better antiproliferative activity than those derived from bioisoteric replacement of furan chalcones (18-29) on MDA-MB231 breast cancer cells. In contrast, the compounds derived from furan chalcones showed generally better antiproliferative activity on MDA-MB468 breast cancer cells. Among 24 compounds examined, compounds 21 and 23 showed significantly improved antiproliferative activity against MDA-MB231 and MDA-MB468 cancer cells. However, compound 23 ((E)-1-(4-chlorophenyl)-3-(5-(4-methoxyphenyl)furan-2-yl)prop-2-en-1-one) is considered to be most desirable among this series, since its antiproliferative activity was 3 to 7-fold higher on cancer than non-cancer cells. Compound 23 showed not only more effective activity than the widely prescribed cisplatin on cancer cells, but it also showed differential antiproliferative activity against cancer cells, a property that is not shown with cisplatin. If this property shown in cell culture stands in vivo test, compound 23 can be an effective and safe anticancer drug. (C) 2012 Elsevier Masson SAS. All rights reserved.