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In vitro and in vivo efficacies of carbazole aminoalcohols in the treatment of alveolar echinococcosis

Dang, Zhisheng, Xu, Shuo, Zhang, Haobing, Gui, Weifeng, Zhao, Yumin, Duan, Liping, Hu, Wei
Acta tropica 2018 v.185 pp. 138-143
Echinococcus multilocularis, albendazole, amino alcohols, cytotoxicity, drug therapy, drugs, echinococcosis, hepatoma, histopathology, kidneys, liver, mebendazole, mice, mortality, protoscoleces, rats, spleen
Benzimidazoles, including albendazole and mebendazole, are the major drugs for clinical chemotherapy of echinococcosis. They mainly exert parasitostatic effects depending on high dosages for long-term. Previous studies have identified carbazole aminoalcohols as novel anti-CE (cystic echinococcosis) agents. However, it is still to be confirmed whether it is effective on alveolar echinococcosis (AE) or not. In the present study, efficacies of novel carbazole aminoalcohols, propylamine, R-propylamine and S-propylamine were evaluated under in vitro and in vivo conditions. Carbazole aminoalcohols were tested against Echinococcus multilocularis (E. multilocularis) protoscoleces (PSC) in vitro. The effects of propylamine and R-propylamine exhibited a time-dependent manner at different concentrations, while the effect of S-propylamine was very poor. At a concentration of 20 μM, the mortality of PSC achieved to 100% on the 11th day after exposure to R-propylamine. The treatment of carbazole aminoalcohols to infected mice resulted in statistically significant reductions in the cyst weights compared with those obtained from negative control mice (p < 0.05), and no significant differences were found between albendazole and carbazole aminoalcohols (p > 0.05). The cytotoxicity examination in rat hepatoma (RH) cells indicated that propylamine and R/S-propylamine were lower that of albendazole at a low concentration (5 μM). In addition, histopathological observation of organs (liver, spleen and kidney) for experimental mice showed mild inflammatory changes in the liver and spleen. This study reveals the potential of carbazole aminoalcohols as a class of novel anti-AE agents.