title: Synthesis and cytotoxic activity of N-[(alkylamino)alkyl]carboxamide derivatives of 7-oxo-7H-benz[de]anthracene, 7-oxo-7H-naphtho[1,2,3-de]quinoline, and 7-oxo-7H-benzo[e]perimidine.
abstract: 7-Oxo-7H-naphtho[1,2,3-de]quinoline-11-carboxamides and analogues were prepared and evaluated for in vitro and in vivo antitumor activity. Chromophore variations included 'deaza' (7-oxo-7H-benz[de]anthracene) and 'diaza' (7-oxo-7H-benzo[e]perimidine) analogues, and side chain variations included chiral alpha-methyl compounds. The naphthoquinolines were the most cytotoxic, with IC(50) values of 5-20 nM, and showed the strongest DNA binding, with high selectivity for G-C rich DNA. The chiral alpha-methyl analogues were 10-20-fold more cytotoxic than the parent des-methyl compound. Both enantiomers provided substantial growth delays against s.c. colon 38 tumors in mice, with the R-enantiomer more active than the S (tumor growth delays of >35 and 12 days, respectively).
authors.affiliation: Chemistry Department, La Trobe University, Victoria 3086, Australia.
authors.forename: Xianyong
authors.initials: X
authors.lastname: Bu
authors.forename: Junjie
authors.initials: J
authors.lastname: Chen
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Deady
authors.forename: Clare L
authors.initials: CL
authors.lastname: Smith
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Baguley
authors.forename: Debra
authors.initials: D
authors.lastname: Greenhalgh
authors.forename: Shangjin
authors.initials: S
authors.lastname: Yang
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009368:Neoplasm Transplantation; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D011804:Quinolines; C022049:perimidine