Antihelminthic activity of some newly synthesized 5(6)-(un)substituted-1H-benzimidazol-2-ylthioacetylpiperazine derivatives

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.     

Protective Effects of a Purified Saponin Mixture from Astragalus corniculatus Bieb., in vivo Hepatotoxicity Models

In this study, the in vivo effects of a purified saponin mixture (PSM), obtained from Astragalus corniculatus Bieb., were investigated using two in vivo hepatotoxicity models based on liver damage caused by paracetamol (PC) and carbon tetrachloride (CCl₄). The effects of PSM were compared with silymarin. Male Wistar rats were challenged orally with 20% CCl₄ or PC (2 g/kg) four days after being pre‐treated with PSM (100 mg/kg) or silymarin (200 mg/kg). A significant decrease of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase (LDH) activities and glutathione (GSH) levels and an increase of malondialdehyde (MDA) quantity was observed after CCl₄ and PC administration alone. PSM pre‐treatment decreased serum transaminases and LDH activities and MDA levels and increased the levels of cell protector GSH. Biotransformation phase I enzymes were also assessed in both models. In the CCl₄ hepatotoxicity model, pre‐treatment with PSM or silymarin resulted in significantly increased activities of ethylmorphine‐N‐demethylase and aniline 4‐hydroxylase activity and cytochrome P450, compared to the CCl₄ only group. Neither silymarin nor PSM influenced PC biotransformation. Our results suggest that PSM, obtained from A. corniculatus, Bieb. showed in vivo hepatoprotective and antioxidant activities against CCl₄ and PC‐induced liver damage comparable to that of silymarin. Copyright © 2012 John Wiley & Sons, Ltd.