Organosulfur compounds as pre-exposure therapy for threat agents.
A series of symmetric (Ar-S-S-Ar) and unsymmetric (Ar-S-S-CH2CH2NH3+Cl-) disulfides have been prepared and evaluated as potential cyanoprotective agents. Target compounds have been prepared by known methods and/or methods developed by us specifically for this program, e.g. reaction of a thiol with 2,2'-dithiobis(benzothiazole) (BT-S-S-BT) followed by reaction with a second thiol. Both 4-methoxyphenyl disulfide and 2-aminoethyl-4-methoxyphenyl disulfide hydrochloride are cyanoprotective against 2-LD50 of injected cyanide. Evaluation of both symmetric and unsymmetric related disulfides indicates that structural requirements for cyanoprotective activity are stringent and strongly suggest that protection is enzyme mediated. In addition to cyanoprotective action, initial results suggest that unsymmetric disulfides may evolve into effective antimustard agents.
Ternay
A L
AL
Center for Medicinal Chemistry, Department of Chemistry and Biochemistry, University of Texas at Arlington, 76019, USA. aternay@du.edu
Brzezinska
E
E
Sorokin
V
V
Cook
C
C
Lyaschenko
Y E
YE
D004220:Disulfides / Q000138:chemical synthesis / Q000494:pharmacology*; D006856:Hydrogen Cyanide / Q000633:toxicity*; D011041:Poisoning / Q000517:prevention & control; D020011:Protective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000494:pharmacology*
D004220:Disulfides; D020011:Protective Agents; D013438:Sulfhydryl Compounds; D006856:Hydrogen Cyanide