Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents

Wen Cai, Mary Hassani, Rajesh Karki, Ervin D. Walter, Katherine H. Koelsch, Hassan Seradj, Jayana P. Lineswala, Hamid Mirzaei, Jeremy S. York, Fatemeh Olang, Minoo Sedighi, Jennifer S. Lucas, Thomas J. Eads, Anthony S. Rose, Sahba Charkhzarrin, Nicholas G. Hermann, Howard D. Beall, Mohammad Behforouz

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

A series of lavendamycin analogues with two, three or four substituents at the C-6, C-7 N, C-2′, C-3′ and C-11′ positions were synthesized via short and efficient methods and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The compounds were prepared through Pictet-Spengler condensation of the desired 2-formylquinoline-5,8-diones with the required tryptophans followed by further needed transformations. Metabolism and toxicity studies demonstrated that the best substrates for NQO1 were also the most selectively toxic to NQO1-rich tumor cells compared to NQO1-deficient tumor cells.

Original languageEnglish (US)
Pages (from-to)1899-1909
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number5
DOIs
StatePublished - Mar 1 2010

Keywords

  • Antitumor
  • Cytotoxicity
  • Lavendamycin analogues
  • NQO1
  • Quinoline-5,8-diones

ASJC Scopus subject areas

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

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  • Cite this

    Cai, W., Hassani, M., Karki, R., Walter, E. D., Koelsch, K. H., Seradj, H., Lineswala, J. P., Mirzaei, H., York, J. S., Olang, F., Sedighi, M., Lucas, J. S., Eads, T. J., Rose, A. S., Charkhzarrin, S., Hermann, N. G., Beall, H. D., & Behforouz, M. (2010). Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents. Bioorganic and Medicinal Chemistry, 18(5), 1899-1909. https://doi.org/10.1016/j.bmc.2010.01.037