title: Design and synthesis of anti-breast cancer agents from 4-piperazinylquinoline: a hybrid pharmacophore approach.
abstract: A novel class of 4-piperazinylquinoline derivatives based on the isatin scaffold were designed by molecular hybridization approach and synthesized for biological evaluation. Subsequently, the compounds were examined for their cytotoxic effects on two human breast tumor cell lines, MDA-MB468 and MCF7, and two non-cancer breast epithelial cell lines, 184B5 and MCF10A. Although all compounds examined were quite effective on the breast cancer cell lines examined, the compound 4-bromo-1-[4-(7-chloro-quinolin-4-yl)-piperazin-1-ylmethyl]-1H-indole-2,3-dione (5b) and N(1)-[4-(7-trifluoromethyl-quinolin-4-yl)]-piperazin-1-ylmethyl-4-chloro-1H-indole-2,3-dione-3-thiosemicarbazone (8a) emerged as the most active among this series. It appeared that both 5b and 8a caused apoptosis to MCF7 cancer cells, but not MCF10A non-cancer cells. Thus, 4-piperazinylquinoline linked isatin analog can serve as the prototype molecule for further development of a new class of anti-breast cancer agents.
authors.affiliation: Tumour Biology Group, Northeastern Ontario Regional Cancer Program at the Sudbury Regional Hospital, Sudbury, Ontario, Canada. rsolomon@hrsrh.on.ca
authors.forename: V Raja
authors.initials: VR
authors.lastname: Solomon
authors.forename: Changkun
authors.initials: C
authors.lastname: Hu
authors.forename: Hoyun
authors.initials: H
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
chemical_list: D000970:Antineoplastic Agents; D010879:Piperazines; D011804:Quinolines