title: Synthesis and biological evaluation of amino-substituted benzo[f]pyrido[4,3-b] and pyrido[3,4-b]quinoxalines: a new class of antineoplastic agents.
abstract: In order to study the structure-activity relationships in the series of new intercalating polycyclic agents, 1-amino-substituted pyrido[3,4-b]quinoxalines, benzo[f]pyrido[4,3-b]quinoxaline derivatives bearing a dibasic side chain and their benzo[f]pyrido[3,4-b] isomers have been synthesized. Biological evaluation was carried out for topoisomerase I and II inhibition, and for in vitro and in vivo antitumor properties in several models. Results demonstrate that appropriately substituted benzo[f]pyrido[4,3-b]quinoxaline derivatives are inhibitors of topoisomerase I and II, and have significant antitumor properties in various experimental models. In addition, the most active compounds appear to be minimally recognized by tumor cells expressing the multidrug resistance phenotype.
authors.affiliation: URA 1387 CNRS, Institut Curie, section de Biologie, Orsay, France.
authors.forename: C H
authors.initials: CH
authors.lastname: Nguyen
authors.forename: E
authors.initials: E
authors.lastname: Fan
authors.forename: J F
authors.initials: JF
authors.lastname: Riou
authors.forename: M C
authors.initials: MC
authors.lastname: Bissery
authors.forename: P
authors.initials: P
authors.lastname: Vrignaud
authors.forename: F
authors.initials: F
authors.lastname: Lavelle
authors.forename: E
authors.initials: E
authors.lastname: Bisagni
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung; D003110:Colonic Neoplasms; D004354:Drug Screening Assays, Antitumor; D007941:Leukemia P388; D051379:Mice; D008810:Mice, Inbred C57BL; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011810:Quinoxalines; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors