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 Citations (Scopus)

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

Fingerprint

Cytotoxicity
Metabolism
Antineoplastic Agents
Tumors
Cells
Poisons
Tryptophan
NAD
Toxicity
Condensation
Neoplasms
Oxidoreductases
Substrates
lavendamycin
In Vitro Techniques
benzoquinone

Keywords

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

ASJC Scopus subject areas

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

Cite this

Cai, W., Hassani, M., Karki, R., Walter, E. D., Koelsch, K. H., Seradj, H., ... 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

Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents. / Cai, Wen; Hassani, Mary; Karki, Rajesh; Walter, Ervin D.; Koelsch, Katherine H.; Seradj, Hassan; Lineswala, Jayana P.; Mirzaei, Hamid; York, Jeremy S.; Olang, Fatemeh; Sedighi, Minoo; Lucas, Jennifer S.; Eads, Thomas J.; Rose, Anthony S.; Charkhzarrin, Sahba; Hermann, Nicholas G.; Beall, Howard D.; Behforouz, Mohammad.

In: Bioorganic and Medicinal Chemistry, Vol. 18, No. 5, 01.03.2010, p. 1899-1909.

Research output: Contribution to journalArticle

Cai, W, Hassani, M, Karki, R, Walter, ED, Koelsch, KH, Seradj, H, Lineswala, JP, Mirzaei, H, York, JS, Olang, F, Sedighi, M, Lucas, JS, Eads, TJ, Rose, AS, Charkhzarrin, S, Hermann, NG, Beall, HD & Behforouz, M 2010, 'Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents', Bioorganic and Medicinal Chemistry, vol. 18, no. 5, pp. 1899-1909. https://doi.org/10.1016/j.bmc.2010.01.037
Cai, Wen ; Hassani, Mary ; Karki, Rajesh ; Walter, Ervin D. ; Koelsch, Katherine H. ; Seradj, Hassan ; Lineswala, Jayana P. ; Mirzaei, Hamid ; York, Jeremy S. ; Olang, Fatemeh ; Sedighi, Minoo ; Lucas, Jennifer S. ; Eads, Thomas J. ; Rose, Anthony S. ; Charkhzarrin, Sahba ; Hermann, Nicholas G. ; Beall, Howard D. ; Behforouz, Mohammad. / Synthesis, metabolism and in vitro cytotoxicity studies on novel lavendamycin antitumor agents. In: Bioorganic and Medicinal Chemistry. 2010 ; Vol. 18, No. 5. pp. 1899-1909.
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