title: Synthesis and topoisomerase I inhibitory activity of a novel diazaindeno[2,1-b]phenanthrene analogue of Lamellarin D.
abstract: A novel 5-oxa-6a,8-diazaindeno[2,1-b]phenanthren-7-one scaffold was designed and synthesized as an active analogue of the cytotoxic marine alkaloid Lamellarin D. The design was based on molecular modeling of the site of interaction of Lamellarin D with DNA-topoisomerase I cleavable complex, whereas the synthesis capitalized on a simple Friedel-Crafts cyclization of indole to a β-carbolinone nucleus. The product exhibited topoisomerase I poisoning activity and submicromolar cytotoxicity on human non-small cell lung cancer H460 cell line.
authors.affiliation: Department of Molecular and Agrifood Sciences, Università di Milano, Via Celoria 2, 20133 Milano, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cananzi
authors.forename: Lucio
authors.initials: L
authors.lastname: Merlini
authors.forename: Roberto
authors.initials: R
authors.lastname: Artali
authors.forename: Giovanni Luca
authors.initials: GL
authors.lastname: Beretta
authors.forename: Nadia
authors.initials: N
authors.lastname: Zaffaroni
authors.forename: Sabrina
authors.initials: S
authors.lastname: Dallavalle
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology; D004264:DNA Topoisomerases, Type I / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008974:Mollusca; D009792:Oceans and Seas; D013539:Simian virus 40 / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D003374:Coumarins; D006576:Heterocyclic Compounds, 4 or More Rings; D007546:Isoquinolines; D059004:Topoisomerase I Inhibitors; C455554:lamellarin D; D004264:DNA Topoisomerases, Type I