Synthesis of amino derivatives of dithio acids as potential radiation-protective agents. Final report, 15 March 1983-14 March 1985

Technical Report · Fri Mar 01 04:00:00 EST 1985

OSTI ID:5529042

Foye, W O

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.

• Research Organization: Massachusetts Coll. of Pharmacy and Allied Health Sciences, Boston (USA)
• OSTI ID: 5529042
• Report Number(s): AD-A-165839/2/XAB
• Country of Publication: United States
• Language: English

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
400301 -- Organic Chemistry-- Chemical & Physicochemical Properties-- (-1987)
560100* -- Biomedical Sciences
Applied Studies-- Radiation Effects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACETIC ACID
ALKOXY RADICALS
ALKYL RADICALS
AMINES
AMINO ACIDS
ANIMALS
AROMATICS
AZAARENES
AZINES
CARBOXYLIC ACIDS
COPPER
DRUGS
ELEMENTS
GLUTATHIONE
HALIDES
HALOGEN COMPOUNDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXYL RADICALS
INACTIVATION
INORGANIC ACIDS
IODIDES
IODINE COMPOUNDS
IRRADIATION
MAMMALS
METALS
METHYL RADICALS
MICE
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
PYRIDINES
QUINOLINES
RADICALS
RADIOPROTECTIVE SUBSTANCES
RODENTS
SULFURIC ACID
SYNTHESIS
THIOIC ACIDS
TRANSITION ELEMENTS
VERTEBRATES
VINYL RADICALS