title: Synthesis of catecholamide spiroarsoranes and their in vitro anthelmintic properties against Molinema dessetae and Nippostrongylus brasiliensis infective larvae.
abstract: Catecholamide spiroarsoranes were synthesized and evaluated for anthelmintic properties on two in vitro models, infective larvae of the filaria Molinema dessetae and infective larvae of an intestinal nematode. Nippostrongylus brasiliensis. On the N dessetae model, the most active compound after 24 h incubation time had an EC50 of 0.1 mumol/l. Eleven compounds had EC50 's in a range from 2 to 200 mumol/l. After 7 days incubation time, the two most active compounds had EC50 's of 0.03 and 0.07 mumol/l, respectively. On the N brasiliensis model, only three compounds were slightly active after 4 days incubation time. The ligands used for the spiroarsoranes synthesis were also evaluated for anthelmintic activity in order to know the contribution of these structures in the spiroarsoranes activity. Spiroarsoranes as prodrugs of arsonic acids were very active on the filaria, nematode having predominantly transcuticular uptake of nutrients while the activity on the intestinal nematode having both the types, transcuticular and intestinal uptake was low. The high sensitivity of filarial infective larvae is probably in relation to their location in the mosquito whereas N. brasiliensis infective larvae are telluric and should be more unsensitive to survive in a variable environment.
authors.affiliation: Université de Paris-Sud, Chatenay-Malabry, France.
authors.forename: P M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: M
authors.initials: M
authors.lastname: Trabelsi
authors.forename: Y
authors.initials: Y
authors.lastname: Madaule
authors.forename: C
authors.initials: C
authors.lastname: Bories
authors.forename: J G
authors.initials: JG
authors.lastname: Wolf
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000494:pharmacology; D001152:Arsenicals / Q000138:chemical synthesis* / Q000494:pharmacology; D005369:Filaricides / Q000138:chemical synthesis / Q000494:pharmacology; D007814:Larva; D008024:Ligands; D009348:Nematoda / Q000187:drug effects*; D009559:Nippostrongylus / Q000187:drug effects*; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000871:Anthelmintics; D001152:Arsenicals; D005369:Filaricides; D008024:Ligands; D011355:Prodrugs