Synthesis and topoisomerase I inhibitory properties of luotonin A analogues

Ali Cagir, Brian M. Eisenhauer, Rong Gao, Shannon J. Thomas, Sidney Hecht

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Luotonin A, a naturally occurring pyrroloquinazolinoquinoline alkaloid, has been previously demonstrated to be a topoisomerase I poison. A number of luotonin A derivatives have now been prepared through the condensation of anthranilic acid derivatives and 1,2-dihydropyrrolo[3,4-b]quinoline-3-one in the presence of phosphorus oxychloride. When dichloromethane was used as solvent the reaction proceeded to a single product. In contrast when the reaction was carried out in tetrahydrofuran or in phosphorus oxychloride, an additional isomeric product was obtained. The luotonin A analogues were evaluated for their ability to effect stabilization of the covalent binary complex formed between human topoisomerase I and DNA, and for cytotoxicity toward a yeast strain expressing the human topoisomerase I.

Original languageEnglish (US)
Pages (from-to)6287-6299
Number of pages13
JournalBioorganic and Medicinal Chemistry
Volume12
Issue number23
DOIs
StatePublished - Dec 1 2004
Externally publishedYes

Fingerprint

Type I DNA Topoisomerase
Derivatives
Poisons
Methylene Chloride
Cytotoxicity
Alkaloids
Yeast
Condensation
Stabilization
Yeasts
luotonin A
phosphoryl chloride

Keywords

  • Camptothecin
  • Luotonin A
  • Structure-activity relationships
  • Topoisomerase I-DNA inhibition

ASJC Scopus subject areas

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

Cite this

Synthesis and topoisomerase I inhibitory properties of luotonin A analogues. / Cagir, Ali; Eisenhauer, Brian M.; Gao, Rong; Thomas, Shannon J.; Hecht, Sidney.

In: Bioorganic and Medicinal Chemistry, Vol. 12, No. 23, 01.12.2004, p. 6287-6299.

Research output: Contribution to journalArticle

Cagir, Ali ; Eisenhauer, Brian M. ; Gao, Rong ; Thomas, Shannon J. ; Hecht, Sidney. / Synthesis and topoisomerase I inhibitory properties of luotonin A analogues. In: Bioorganic and Medicinal Chemistry. 2004 ; Vol. 12, No. 23. pp. 6287-6299.
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