Potentiation of fasciolicidal agents by benzoyl side chains. Synthesis of benzoylsalicylanilides.
The synthesis and potent fasciolicidal activity of novel salicylanilides, with benzoyl substituents in the salicyl ring, is described. Several compounds surpassed the activity of commercially used flukicides against Fasciola hepatica infections in rats. Compounds 10, 11, and 15 were poorly active against the parasite in sheep and inactive in infected calves. It is concluded that the benzoyl substituents potentiate antiparasitic action by virtue of their electron-withdrawing properties rather than by advantageous protein binding at parasite receptor sites. Poor activity in sheep is ascribed to in vivo reduction of the carbonyl in the benzoyl group of the anilides.
D000818:Animals; D001565:Benzoates / Q000138:chemical synthesis / Q000627:therapeutic use; D004357:Drug Synergism; D005210:Fasciola hepatica; D005211:Fascioliasis / Q000188:drug therapy*; D051381:Rats; D012457:Salicylamides / Q000138:chemical synthesis*; D012458:Salicylanilides / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D001565:Benzoates; D012457:Salicylamides; D012458:Salicylanilides