title: 2-substituted 1H-pyrrolo [3,2-h] quinoline derivatives: synthesis and aspects of their biological activity.
abstract: Certain 2-substituted 1H-pyrrolo [3,2-h] quinolines have been prepared and their biological activity in mammalian cells and in some microorganisms have been studied. These compounds represent a simplified ellipticine heterocyclic moiety: in addition they have a different ring condensation, leading to an angular molecular structure instead of a linear one. In mammalian cells all compounds appeared to be able of inducing an antiproliferative effect and an extensive DNA fragmentation, similarly to ellipticine, even if to a reduced extent. The new derivatives behaved in a comparable way also on some microorganisms, such as T2 bacteriophage (which appears to be less sensitive than mammalian cells) and in mutagenesis tests carried out with E. coli WP2 TM9 and S. typhimurium TA 98, which are reverted by base substitution and frame-shift mutagens, respectively. Similarly to the reference compound, all ellipticine analogues appeared to be no mutagenic. The obtained results suggest that they induce the antiproliferative activity in mammalian cells mainly as topoisomerase inhibitors, similarly to ellipticine itself. Therefore, they represent an interesting model to design new potential anticancer drugs.
authors.affiliation: Department of Pharmaceutical Sciences, Padua University, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Ferlin
authors.forename: G
authors.initials: G
authors.lastname: Chiarelotto
authors.forename: F
authors.initials: F
authors.lastname: Baccichetti
authors.forename: F
authors.initials: F
authors.lastname: Carlassare
authors.forename: L
authors.initials: L
authors.lastname: Toniolo
authors.forename: F
authors.initials: F
authors.lastname: Bordin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D016368:Frameshift Mutation / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D009152:Mutagenicity Tests; D009153:Mutagens / Q000138:chemical synthesis / Q000633:toxicity; D011758:Pyrroles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013604:T-Phages / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D009153:Mutagens; D011758:Pyrroles; D011804:Quinolines