Design, synthesis and biological study of new antiparasitic spiroarsoranes.
Thirty-eight new spiroarsoranes were synthesized after structure-activity relationship studies from the first series. These compounds were predicted to cross more easily the membrane of protozoae or the cuticle of Nematodes and to reach their biological target with efficiency. The spiroarsoranes were evaluated for their antiparasitic properties, on helminths and protozoa models in regard of their parent arsonic acids. The following parasite models were used: Entamoeba histolytica and Trichomonas vaginalis in vitro; Molinema dessetae infective larvae in vitro, adults and microfilariae in vivo; Nippostrongylus brasiliensis infective larvae in vitro. The results obtained on these models indicated that the "spiranization" of arsonic acids produced new compounds with a biological activity 10-fold superior to those of arsonic acids. Nevertheless, each parasite had its own sensitivity to spiroarsoranes. Moreover, in vivo results showed that the lipophilicity of the molecules should be optimal to avoid high toxicity in host such as arsenical encephalopathy.
Loiseau
P M
PM
Faculté de Pharmacie, Université de Paris-Sud, France.
Rekik
L
L
Madaule
Y
Y
Gayral
P
P
Wolf
J G
JG
D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis* / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001152:Arsenicals / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D015195:Drug Design; D004748:Entamoeba histolytica / Q000187:drug effects; D005260:Female; D005368:Filariasis / Q000188:drug therapy / Q000469:parasitology; D005369:Filaricides / Q000494:pharmacology; D007814:Larva; D008055:Lipids / Q000737:chemistry; D008297:Male; D009559:Nippostrongylus / Q000187:drug effects; D051381:Rats; D012377:Rodentia; D012995:Solubility; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014246:Trichomonas vaginalis / Q000187:drug effects
D000871:Anthelmintics; D000981:Antiprotozoal Agents; D001152:Arsenicals; D005369:Filaricides; D008055:Lipids; D013141:Spiro Compounds