Synthesis and in vitro anthelmintic properties of some new dithiaarsanes

Fifteen new trivalent organoarsenicals were synthesized and evaluated for a nthelmintic properties on three in vitro models, infective larvae of the fi laria Molinema dessetae, infective larvae of an intestinal nematode, Nippos trongylus brasiliensis and adults and larvae of Rhabditis pseudoelongata a free living nematode. On the M. dessetae model, the most active compound af ter a 24 h incubation period had an EC50 of 0.02 mu mol/l (compound 3a). Tw elve compounds had an EC50 lower than 1 mu mol/l whereas potassium melarson yl exhibited an EC50 of 45.6 mu mol/l. After 7 days incubation time, compou nd 1d had an EC50 of 2 nmol/l. On the N. brasiliensis model, compound 1d wa s also the most efficient after a 4 day incubation period (EC50 of 1 mu mol /l). This compound was 100 times more active than potassium melarsonyl used as a reference compound. Nevertheless, no compound had an EC50 less than 1 00 mu mol/l on Rhabditis pseudoelongata. Concerning the effect of dithiol ligands on the anthelmintic activity of th ese trivalent organoarsenicals on M. dessetae and N. brasiliensis, 2,2'-dim ercaptodiethyloxide was more efficient as dithiol ligand than 1,3-dimercapt opropane which was more efficient than 1,2-dimercaptoethane. Moreover, the para-amino haptophore was more efficient than the melaminyl haptophore. The se results showed that the use of new dithiol ligands for trivalent arsenic als enhanced greatly the anthelmintic activity compared with potassium mela rsonyl.