RELATIONSHIPS BETWEEN THE ANTHELMINTIC ACTIVITY OF EIGHT DERIVATIVES OF BENZIMIDAZOLE CARBAMATES AGAINST TRICHINELLA SPIRALIS AND THEIR CHEMICAL STRUCTURES

Abstract

Efficacy of eight recently developed and used anthelmintics of the benzimidazole carbamates; mebendazole, flubendazole, oxfendazole, albendazole, oxibendazole, 790163 proflubendazole, 780118 “cyanide” benzimidazole and 780120 “selenium” benzimidazole was tested orally against the enteral immature larval and adult stages of Trichinella spiralis in mice. Six of these derivatives of methyl benzimidazole-2-carbamates have an aryl and two have an alkyl substituent at the 5'-position of the parent benzimidazole ring. The nature of these substituents was found to be related to the antitrichinellous activity of the compounds. Compounds with the 5'-substituent linked to the parent benzimidazole ring by either a carbon, sulfur or an oxygen atom are more potent than those bridged by selenium or by the carbon with an attached -CN group. The result clearly indicates that the benzimidazoles are invariably more potent against immature enteral phase than the adult worms. This finding would be of importance in a targeted synthesis of new, effective derivatives of benzimidazole, e.g., in the screening for more important tissue-dwelling nematodes like filarial worms.