Synthesis and in vitro anthelmintic properties of some new dithiaarsanes.
Fifteen new trivalent organoarsenicals were synthesized and evaluated for anthelmintic properties on three in vitro models, infective larvae of the filaria Molinema dessetae, infective larvae of an intestinal nematode, Nippostrongylus brasiliensis and adults and larvae of Rhabditis pseudoelongata a free living nematode. On the M. dessetae model, the most active compound after a 24 h incubation period had an EC50 of 0.02 mumol/l (compound 3a). Twelve compounds had an EC50 lower than 1 mumol/l whereas potassium melarsonyl exhibited an EC50 of 45.6 mumol/l. After 7 days incubation time, compound 1d had an EC50 of 2 nmol/l. On the N. brasiliensis model, compound 1d was also the most efficient after a 4 day incubation period (EC50 of 1 mumol/l). This compound was 100 times more active than potassium melarsonyl used as a reference compound. Nevertheless, no compound had an EC50 less than 100 mumol/l on Rhabditis pseudoelongata. Concerning the effect of dithiol ligands on the anthelmintic activity of these trivalent organoarsenicals on M. dessetae and N. brasiliensis, 2,2'-dimercaptodiethyloxide was more efficient as dithiol ligand than 1,3-dimercaptopropane which was more efficient than 1,2-dimercaptoethane. Moreover, the para-amino haptophore was more efficient than the melaminyl haptophore. These results showed that the use of new dithiol ligands for trivalent arsenicals enhanced greatly the anthelmintic activity compared with potassium melarsonyl.
Loiseau
P M
PM
Université de Paris-Sud, Châtenay-Malabry, France.
Lubert
P
P
Wolf
J G
JG
D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001151:Arsenic / Q000737:chemistry / Q000494:pharmacology*; D005368:Filariasis / Q000188:drug therapy / Q000469:parasitology; D007814:Larva / Q000187:drug effects; D008024:Ligands; D009349:Nematode Infections / Q000188:drug therapy / Q000469:parasitology; D009559:Nippostrongylus; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017172:Rhabditoidea
D000871:Anthelmintics; D008024:Ligands; D009942:Organometallic Compounds; D001151:Arsenic