title: Synthesis and antiproliferative activity of some ellipticine-like 11H-pyrido[a]carbazole derivatives.
abstract: Some modified 11H-pyrido[a]carbazoles (11H-PyC) and their corresponding tetrahydro derivatives (11H-THPyC) were prepared. A common multistep pathway characterized by conventional reactions, including a Fischer-indole-type synthesis, yielded the tetracyclic compounds. To improve cytotoxicity, 11H-PyC and 11H-THPyC derivatives were endowed with a diethylaminoethyl side chain. The antiproliferative activity was assessed in three human tumor cell lines, and a number of derivatives showed a cytotoxic effect in agreement with their capacity to form a molecular intercalative complex with DNA and to interfere with the relaxation activity of DNA topoisomerase II. In contrast, three derivatives that exhibited significant antiproliferative efficacy, showed no inhibition of topoisomerase II, thus suggesting an unexpected and novel mode of action for these ellipticine-like compounds independent of topoisomerase II activity.
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Padova, Via Marzolo 5, 35131 Padova, Italy. mariagrazia.ferlin@unipd.it
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ferlin
authors.forename: Ornella
authors.initials: O
authors.lastname: Gia
authors.forename: Lisa
authors.initials: L
authors.lastname: Dalla Via
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D004611:Ellipticines / Q000737:chemistry*; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D004611:Ellipticines; D007364:Intercalating Agents; D059005:Topoisomerase II Inhibitors; C041514:carbazole; C034192:ellipticine; D004247:DNA; D004250:DNA Topoisomerases, Type II