title: Anti-breast cancer activity of heteroaryl chalcone derivatives.
abstract: 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.
authors.affiliation: Tumor Biology Group, Northeastern Ontario Regional Cancer Program, Regional Hospital, 41 Ramsey Lake Road, Sudbury, Ontario, Canada.
authors.forename: V Raja
authors.initials: VR
authors.lastname: Solomon
authors.forename: Hoyun
authors.initials: H
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002599:Chalcone