title: Antitumor agents. 181. Synthesis and biological evaluation of 6,7,2',3',4'-substituted-1,2,3,4-tetrahydro-2-phenyl-4-quinolones as a new class of antimitotic antitumor agents.
abstract: A novel series of 6,7,2',3',4'-substituted-1,2,3,4-tetrahydro-2-phenyl- 4-quinolones were synthesized and evaluated for interactions with tubulin and for cytotoxic activity against a panel of human tumor cell lines, including ileocecal carcinoma (HCT-8), breast cancer (MCF-7), lung carcinoma (A-549), epidermoid carcinoma of the nasopharynx (KB), renal cancer (CAKI-1), and melanoma cancer (SKMEL-2). Most compounds (18, 20, 22-27) showed potent cytotoxic and antitubulin effects. The most active compounds (23, 26, 27) demonstrated strong cytotoxic effects with ED50 values in the nanomolar or subnanomolar range in almost all tumor cell lines. Three active racemates (20, 22, 25) were separated into the enantiomers, and generally, the optically pure (-)-isomers (20a, 22a, 25a) exhibited greater biological activity than the racemates or (+)-isomers. Cytotoxicity and antitubulin activity were closely correlated, with the most active compounds (23, 26, 27) having effects comparable to those of colchicine, podophyllotoxin, and combretastatin A-4.
authors.affiliation: Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill 27599, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xia
authors.forename: Z Y
authors.initials: ZY
authors.lastname: Yang
authors.forename: P
authors.initials: P
authors.lastname: Xia
authors.forename: K F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Y
authors.initials: Y
authors.lastname: Tachibana
authors.forename: S C
authors.initials: SC
authors.lastname: Kuo
authors.forename: E
authors.initials: E
authors.lastname: Hamel
authors.forename: T
authors.initials: T
authors.lastname: Hackl
authors.forename: K H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D015363:Quinolones; D014404:Tubulin