title: Antiproliferative activity of some unsubstituted angular analogoues of ellipticine.
abstract: With the aim of obtaining further knowledge on the antiproliferative activity of pyrroloquinolines and isoquinolines, we prepared four unsubstituted angular pyridotetrahydrocarbazoles having a fourth non-aromatic ring, via modified Fischer synthesis. These compounds may be considered as simpler analogues of ellipticine. They induced evident antiproliferative effects in Ehrlich ascites and in CHO cells in vitro, but were ineffective on T2 bacteriophage. These compounds formed molecular complexes with DNA in vitro, while in CHO cells in vivo, they induced double-strand breaks in DNA and DNA-protein cross-links. These data suggest that these ellipticine analogoues are capable of inhibiting topoisomerase II, as the parent compound does. The most active derivative was 2N-5H-6,7,8,9-tetrahydropyrido[2,3-a]carbazole, which represents an interesting model for the study of new antitumor drugs.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Ferlin
authors.forename: G
authors.initials: G
authors.lastname: Chiarelotto
authors.forename: C
authors.initials: C
authors.lastname: Marzano
authors.forename: S
authors.initials: S
authors.lastname: Mobilio
authors.forename: F
authors.initials: F
authors.lastname: Carlassare
authors.forename: F
authors.initials: F
authors.lastname: Baccichetti
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016466:CHO Cells; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects*; D002942:Circular Dichroism; D006224:Cricetinae; D004247:DNA / Q000187:drug effects; D004611:Ellipticines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D017900:Myoviridae / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D004611:Ellipticines; D007364:Intercalating Agents; D004247:DNA