Radioprotective action of thiadiazole derivatives
Continuing previous investigations on the search for radioprotectors among the sulfurcontaining heterocycles [i, 2], we synthesized and studied the radioprotective properties of derivatives of 1,3,4and 1,2,4-thiadiazoles with various substituents: amino groups, alkyls, and mercapto groups. The following thiadiazole derivatives were investigated: 2alkylamino-5-alkyl-l,3,4-thiadiazoles and their methiodides (I-VII); 2-alkylamino-l,3,4thiadiazole-5-thiones (VIII-XII); 2-alkylamino-5-alkylmercapto-l,3,4-thiadiazoles (XIIIXVIII); 2,5-diamino-l,3,4-thiadiazole and its methiodide (XIX, XX), and 1,2,4-thiadiazoles (XXI-XXIII).
Synthèse et évalutaion de nouveaux composés organiques et phosphorés contre les effets des rayonnements ionisants. Etude de leur mécanisme d'action in vitro.
Ce travail s'inscrit dans un programme de recherche visant a synthetiser de nouveaux composes organiques et phosphores possedant un rapport activite/toxicite convenable. Pour cela, nous avons realise la synthese de nouveaux motifs N-substitues du benzothiazole et du thiadiazole tels que des thiols, aminothiols, acides thiosulfoniques et phosphorothioates. Tous ces composes ont ete caracterises physico-chimiquement par spectroscopie RMN (proton, carbone, phosphore, 2D), par spectrometrie de masse, analyse elementaire et pour certains d'entre eux par diffraction des rayons X. L'activite de la plupart des composes a ete evaluee par des tests in vitro. Les resultats experimentaux ont ete confirmes par des calculs theoriques de DFT visant a etudier le mecanisme de capture des radicaux libres par nos composes. D'autre part, une etude de relation structure activite (QSAR) a ete realisee. Les resultats nous ont permis d'elaborer un modele permettant d'etablir une relation structure-activite.
Chemical protection against ionizing radiation. II. Mercaptoalkylamines and related compounds with protective activity.
The wide search for simple chemicals that would offer some protection to mammals against the damaging effects of radiation has included representatives of most classes of biochemically active compounds. The discovery by Patt et al. (1) that cysteine and glutathione afforded protection to rats spurred the examination by Bacq and associates (2, 3) of both amines and sulfhydryl compounds for protective activity and led to the discovery of 2-mercaptoethylamine (MEA). MEA, as well as its disulfide, provided good protection to mice, in terms of survival, against a lethal dose of whole-body X-radiation. It also markedly reduced the radiosensitivity of bacteria when added to bacterial suspensions before irradiation (4). We initiated an investigation of nitrogenand sulfur-containing substances related to MEA in an attempt to define, by variation in chemical structure, the necessary parameters for maximum protective activity. In addition, we hoped to find a more active compound that might give some insight into the chemical and biochemical processes affected by this type of chemical protective agent. The extensive modifications of the structure of MEA made with the retention of protective activity were presented in a preliminary report (5). Since this work was started, other studies on the effectiveness of mercaptans (6-9) and dithiocarbamates (10) have appeared. This report describes the effect of structural changes on the activity of some thirty representative nitrogenand sulfur-containing compounds. A survey of the more effective mercaptoalkylguanidines formed, via a cyclic transguanylation reaction of the aminoalkylisothiuronium compounds at neutral pH's, is presented in the succeeding paper (11).