ABSTRACT
Piperazine derivatives of 5(6)-substituted-(1H-benzimidazol-2-ylthio)acetic acids were synthesized by using two methods and studied for antihelminthic activity. The antiparasitic screening showed that compounds 18-24 exhibited higher activity against Trichinella spiralis in vitro in comparison to methyl 5-(propylthio)-1H-benzimidazol-2-yl-carbamate (albendazole). Most active were compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21 and 2-{[2-oxo-2-(4-benzhydrylpiperazin-1-yl)ethyl]thio}-5(6)-methyl-1(H)-benzimidazole 19 as well as 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 with efficacy of 96.0%, 98.4% and 100%, respectively. The tested derivatives 15-19 and 20-23 were less active against Syphacia obvelata in vivo than albendazole and exhibited the same efficacy as piperazine, but in twice lower concentration.Compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21, 1,4-bis[(5(6)-methyl-1(H)-benzimidazol-2-ylthio)acetyl]piperazine 17 and 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 had higher efficacies of 73%, 76%, and 77%, respectively.
Subject(s)
Anthelmintics/pharmacology , Benzimidazoles/pharmacology , Oxyuroidea/drug effects , Trichinella spiralis/drug effects , Animals , Anthelmintics/adverse effects , Anthelmintics/chemical synthesis , Anthelmintics/chemistry , Benzimidazoles/adverse effects , Benzimidazoles/chemical synthesis , Benzimidazoles/chemistry , Liver/drug effects , Magnetic Resonance SpectroscopyABSTRACT
Some new thiazolo[3,2-a]benzimidazolone derivatives were synthesized using two methods. The structures of the synthesized compounds were proved by means of IR, (1)H NMR and mass spectral data. Ab initio computations were performed in order to determine the electronic structure and geometry of the investigated molecules and to compare it to the geometry of albendazole. Biologically, experiments in vitro and in vivo were accomplished in order to identify the efficacy of the obtained thiazolobenzimidazolones against Trichinella spiralis. The effectiveness of compounds 4a-c in the intestinal phase of trichinellosis was 100% and in the muscle phase were 88% and 80% at a concentration of 100mg/kg mw for the compounds 4a and 4c. The results of the hepatotoxicity test showed that the compounds 4a and 4b possess hepatotoxicity comparable to that of albendazole.
