title: Highly cytotoxic benzo[c]pyrido[2,3,4-kl]acridines.
abstract: Several benzo[c]pyrido[2,3,4-kl]acridines bearing different substituents on the A and E rings were synthesized and evaluated for their capacity to bind to DNA and to inhibit DNA topoisomerases. Potent cytotoxic compounds were discovered but no strict correlation with their DNA binding affinity and effects on topoisomerases were observed. DNA is one but not the unique target of these compounds.
authors.affiliation: Institut de Chimie Pharmaceutique Albert Lespagnol, EA 2692, Université de Lille 2, BP 83, 59006 Lille, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Chackal
authors.forename: Michael
authors.initials: M
authors.lastname: Facompré
authors.forename: Raymond
authors.initials: R
authors.lastname: Houssin
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Goossens
authors.forename: Nicole
authors.initials: N
authors.lastname: Pommery
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hénichart
authors.forename: Christian
authors.initials: C
authors.lastname: Bailly
mesh_terms: D000166:Acridines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D004247:DNA / Q000378:metabolism; D026942:DNA Topoisomerases / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008297:Male; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D011471:Prostatic Neoplasms / Q000188:drug therapy; D059003:Topoisomerase Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059003:Topoisomerase Inhibitors; D004247:DNA; C427203:calf thymus DNA; D026942:DNA Topoisomerases