2012
DOI: 10.2174/092986712803988802
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Chemistry and Pharmacology of Imexon and Related Cyanoaziridines

Abstract: Following the demonstration that addition of a 2-cyano group to aziridines prevented DNA alkylation and thus reduced toxicity, many novel 2-cyanoaziridines were synthesized and evaluated as immunomodulating and antitumor agents. They typically reacted with thiols such as cysteine, depleting them and allowing the accumulation of reactive oxygen species. Two of these compounds, azimexon and ciamexon, showed activity against tumors in clinical trials. Imexon was produced by cyclization of 2-cyanoaziridine-1- carb… Show more

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Cited by 7 publications
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“…However, in contrast to the initial findings, these cyanoaziridines showed no alkylating activity in vitro or in vivo [ 4 ]. These results suggest that the cyano group reduces the reactivity required for the alkylation of DNA bases and that they may selectively react with sulfur moieties in biological thiols such as cysteine, depleting the stores of cysteine and glutathione and subsequently allowing the accumulation of cellular reactive oxygen species (ROS) [ 6 , 7 , 8 ]. Preclinical studies have evaluated the antitumor activity and the mechanism of action of cyanoaziridine AMP423 ( Ib , Figure 1 ) [ 6 ].…”
Section: Introductionmentioning
confidence: 99%
“…However, in contrast to the initial findings, these cyanoaziridines showed no alkylating activity in vitro or in vivo [ 4 ]. These results suggest that the cyano group reduces the reactivity required for the alkylation of DNA bases and that they may selectively react with sulfur moieties in biological thiols such as cysteine, depleting the stores of cysteine and glutathione and subsequently allowing the accumulation of cellular reactive oxygen species (ROS) [ 6 , 7 , 8 ]. Preclinical studies have evaluated the antitumor activity and the mechanism of action of cyanoaziridine AMP423 ( Ib , Figure 1 ) [ 6 ].…”
Section: Introductionmentioning
confidence: 99%