Reversing the adverse biochemical effects in lead-intoxicated rats by N,N`- bis[(1,2-didehydro-1-hydroxy-2-thioxopyrid-4-yl)-carbonyl]- L-lysine.

N,N`-Bis[(1,2-didehydro-1-hydroxy-2-thioxopyrid-4-yl)-carbonyl]- L-lysine (HTPL) is a novel newly synthesized compound intended to be used for the chelation of lead in intoxicated animals. Subchronic lead intoxication experiments were carried out on Wistar male rats; these rats were intoxicated with lead and then treated with HTPL. Results were compared with those obtained with known compounds used for lead chelation therapy, such as disodium ethylnediaminetetraacetic acid (CaNa2EDTA) and meso-2,3-dimercaptosuccininc acid (DMSA), using different routes of administration. Biological samples of whole blood and urine were collected and analyzed for urinary proporphyrins, δ-aminolevulinic acid dehydratase, and zinc protoporphyrin. Results revealed that HTPL can remarkably reverse the toxic effects of lead intoxication at biochemical levels. Additionally, results showed that this agent is as good or even more potent than calcium disodium ethylnediaminetetraacetic acid (CaNa2EDTA) and meso-2,3-dimercaptosuccininc acid (DMSA) in reversing the toxic effect of lead. More importantly, HTPL was found effective when administrated intraperitoneally and orally.

Synthesis and characterization of new 1-hydroxy-2-pyridinethione derivatives: Their lead complexes and efficacy in the treatment of acute lead poisoning in rats.

A number of new mono- and dihydroxypyridinethione ligands have been synthesized via reaction of dimethylamine and amino acid esters with the active amide obtained from the reaction of 1-hydroxy-2-pyridinethione-4-carboxylic acid (1) and 1,1'-carbonyldiimidazole in DMF. Moreover, the lead complexes of these new ligands were also prepared. Structures of the newly synthesized compounds have been confirmed by different spectroscopic methods such as IR, 1H NMR, and 13C NMR, and by elemental analysis. The effect of these synthesized ligands on the excretion of lead, iron, and zinc, and their distribution in kidneys, liver, and bones in acutely intoxicated rats was investigated and results, for lead, were compared with those of the known drug meso-2,3-dimercaptosuccinic acid (DMSA). Results obtained revealed that compound 5 exhibits remarkable ability in total fecal and urinary excretion of lead and was superior to DMSA. In addition, results show that the concentration of lead in soft tissues and bones was lower in rats treated with HTPL than those treated with DMSA. Furthermore, the concentration of lead in liver tissues obtained from sub-chronic lead-intoxicated rats treated with HTPL was lower than those treated with DMSA and calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA).