Chemical Basis for the Biological Activity of Imexon and Related Cyanoaziridines

Bhashyam S. Iyengar, Robert T Dorr, William A. Remers

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Chemical aspects of mode of action of imexon and related cyanoaziridines were studied. These compounds do not alkylate DNA nor react with the ε-amino groups of L-lysine, despite the presence of an aziridine ring. They do react readily with biologically important sulfhydryl compounds to give products derived from either aziridine ring opening, interaction with the cyano group of cyanoaziridines, or opening of the iminopyrrolidone ring of imexon. The products from reactions of imexon and related cyanoaziridines with thiols are not as potent as their parent compounds against tumor cells. These results are consistent with biological studies that show that the mechanism of cytotoxicity involves thiol depletion followed by oxidative stress leading to apoptosis.

Original languageEnglish (US)
Pages (from-to)218-223
Number of pages6
JournalJournal of Medicinal Chemistry
Volume47
Issue number1
DOIs
StatePublished - Jan 1 2004

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Bioactivity
Sulfhydryl Compounds
Oxidative stress
Cytotoxicity
Lysine
Tumors
Oxidative Stress
Cells
Apoptosis
DNA
4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one
Neoplasms
aziridine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Chemical Basis for the Biological Activity of Imexon and Related Cyanoaziridines. / Iyengar, Bhashyam S.; Dorr, Robert T; Remers, William A.

In: Journal of Medicinal Chemistry, Vol. 47, No. 1, 01.01.2004, p. 218-223.

Research output: Contribution to journalArticle

Iyengar, Bhashyam S. ; Dorr, Robert T ; Remers, William A. / Chemical Basis for the Biological Activity of Imexon and Related Cyanoaziridines. In: Journal of Medicinal Chemistry. 2004 ; Vol. 47, No. 1. pp. 218-223.
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