Synthesis and topoisomerase i inhibitory activity of a novel diazaindeno[2,1-b]phenanthrene analogue of Lamellarin D

Salvatore Cananzi, Lucio Merlini, Roberto Artali, Giovanni Luca Beretta, Nadia Zaffaroni, Sabrina Dallavalle

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4971-4984
Number of pages14
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number16
DOIs
Publication statusPublished - Aug 15 2011

Fingerprint

Type I DNA Topoisomerase
Cells
Molecular modeling
Cyclization
Cytotoxicity
Alkaloids
Scaffolds
Non-Small Cell Lung Carcinoma
Poisoning
Cell Line
lamellarin D
phenanthrene
indole

Keywords

  • Antitumor
  • Lamellarin
  • Molecular modeling
  • Synthesis
  • Topoisomerase I

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Synthesis and topoisomerase i inhibitory activity of a novel diazaindeno[2,1-b]phenanthrene analogue of Lamellarin D. / Cananzi, Salvatore; Merlini, Lucio; Artali, Roberto; Beretta, Giovanni Luca; Zaffaroni, Nadia; Dallavalle, Sabrina.

In: Bioorganic and Medicinal Chemistry, Vol. 19, No. 16, 15.08.2011, p. 4971-4984.

Research output: Contribution to journalArticle

Cananzi, Salvatore ; Merlini, Lucio ; Artali, Roberto ; Beretta, Giovanni Luca ; Zaffaroni, Nadia ; Dallavalle, Sabrina. / Synthesis and topoisomerase i inhibitory activity of a novel diazaindeno[2,1-b]phenanthrene analogue of Lamellarin D. In: Bioorganic and Medicinal Chemistry. 2011 ; Vol. 19, No. 16. pp. 4971-4984.
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