Search for Radioprotective Compounds. Part XVIII. Synthesis and Protective Activity of a Series of S-Omega(Omega-(Omega-Aminoalkylamino) Alkylamino) Alkylphosphorothioic Acids and Disulphides

摘要

The synthesis of the polyamines phosphorothioic acids NH2(CH2)n''NH(CH2)n'NH(CH2)nSPO3H were achieved where n = 2 and 3, n' = 2, 3, 4 and 5; n'' = 2, 3, 4. The toxicities and radiation dose reduction factors (DRF) were determined in mice. The compounds were given intraperitoneally before irradiation. The mice were irradiated with Cs134 gamma radiation source at dose rate of approximately 90 r/min. The best DRF (1.8) was obtained for the compounds with n = n' = n'' = 2 and when n = n'' = 2 and n' = 3. The toxicity increased and protective activity decreased when the number of carbon atoms in the alkyl chains was increased. The preparation of pure thiol derivatives was not totally successful. The one impure thiol compound when n = n' = n'' = 2 obtained had a DRF of 1.41. The disulfide derivatives were prepared but were more toxic and less protective than the parent compounds. The compounds were not protective when given orally or after irradiation. The relationship between chemical structure and radiation protective activity is discussed. (Author)