Highly cytotoxic benzo[c]pyrido[2,3,4-kl]acridines.
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.
Chackal
Sarah
S
Institut de Chimie Pharmaceutique Albert Lespagnol, EA 2692, Université de Lille 2, BP 83, 59006 Lille, France.
Facompré
Michael
M
Houssin
Raymond
R
Goossens
Jean-François
JF
Pommery
Nicole
N
Hénichart
Jean-Pierre
JP
Bailly
Christian
C
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
D000166:Acridines; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059003:Topoisomerase Inhibitors; D004247:DNA; C427203:calf thymus DNA; D026942:DNA Topoisomerases