Synthesis of Amino Derivatives of Dithio Acids as Potential Radiation Protective Agents.
Abstract
Good radiation-protective properties (>50% survival of irradiated mice) were found in a series of N-methylquinolinium-2-dithioacetic acid derivatives at exceptionally low dosage levels (2-10 mg/kg). The most effective compounds were the bis(2-methylthio)-vinyl- and (2-methylthio amino)-vinyl-N-methylquinolinium iodides, which apparently are not active as H atom transfer agents. Addition of longer chain amino functions, containing hydroxy, alkoxy, or additional amino groups did not improve activity. Similar activities were found in a series of N-methylpyridinium-2-dithioacetic acid derivatives, the most active being the 2-methylthio piperidino compound. Further modification of both the methylthio and amino functions to increase lipophilicity did not improve protective activity. No activity was found with a couple of aminocyclopentenedithio acids, but moderate protective activity was found in a series of 3-amino-2-aryldithiopropenoates. No activity was found in the 4-aryl-dithiole-3-thione precursors, known to raise glutathione levels in cells. Reduction to the 3-amino-2-phenylpropanedithio acid bis(methyl) esters gave an inactive compound in the one example tested. Preparation of a copper complex of N-methyl-2-bis(2-methylthio)vinylquinolinium iodide gave a compound having only a little less activity than the uncomplexed compound, indicating that the bis(methylthio) and methylthio amino derivatives of the quinolinium and pyridinium dithioacetic acids may be acting as copper complexes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 1985
- Accession Number
- ADA165839
Entities
People
- William O. Foye