Synthesis of potential prophylactic agents against cyanide intoxication. Annual report, 3 September 1992-3 August 1993
The goal of the proposed research is to provide prophylaxis against cyanide through its sequestration by covalent bond formation. Three strategies were pursued: (1) sulfur-rich compounds which could serve as sulfane sulfur donors to rhodanese and other sulfur transferases; (2) compounds containing multiple carbonyl moieties, including analogs of pyruvate and alpha-ketoglutarate, which can bind cyanide through cyanohydrin formation; and (3) additional classes of compounds that can directly react with cyanide, such as (1) N-alkoxy and N-alkylthio heterocycles, and (2) phthalocyanines and porphyrins. During this report period we prepared examples of all compound types just described. The 33 new compounds submitted this period were distributed among these compound classes as follows: sulfur-rich species, 12; polycarbonyl compounds, 13; nitrogenous heterocycles, 1; and metal complexes, 7. Some of these compounds contained multiple functionality that could react with cyanide. One of the sulfur compounds was prepared at the request of the CO and was a re-submission of an additional quantity of a previously submitted sample which had displayed positive biological results during screening (SoRI 7638; WR 268831). We have received biological testing data for 20 compounds during this same period, and now have demonstrated activity in three of our four primary target classes (no phthalocyanines have been tested for efficacy at this point). Of these 20 screened compounds, the S-sulfo derivative of cysteine (SoRI 7913; WR000125AC) was found to have potential as an improved pretreatment for NaCN poisoning. Anticyanide agents, Polysulfides, Sulfurtransferases (Rhodanese), Cyanohydrin formation, Compounds reactive toward cyanide, Cyanide removal through covalent bonding, RA V.
- Research Organization:
- Southern Research Inst., Birmingham, AL (United States)
- OSTI ID:
- 451278
- Report Number(s):
- AD-B--174761/7/XAB; CNN: Contract DAMD17-90-C-0011
- Country of Publication:
- United States
- Language:
- English
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