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硫代-咪唑烷类化合物的抗血吸虫作用:超微结构和细胞毒性研究。

Antischistosomal action of thioxo-imidazolidine compounds: an ultrastructural and cytotoxicity study.

机构信息

Laboratório de Planejamento e Síntese de Fármacos (LPSF), Departamento de Antibióticos, Centro de Ciências Biológicas, Universidade Federal de Pernambuco (UFPE), Av. Prof. Moraes Rego s/n, Cidade Universitária, Recife, PE, Brazil.

出版信息

Exp Parasitol. 2011 May;128(1):82-90. doi: 10.1016/j.exppara.2011.01.021. Epub 2011 Feb 16.

Abstract

Schistosomiasis is a disease caused by helminthes of the genus Schistosoma, which threatens approximately 207 million people worldwide. Recently, strains of Schistosoma mansoni appear to be developing tolerance and resistance against Praziquantel, the most commonly available drug on the market used in the treatment of disease. This worrisome development justifies studies that seek alternatives for the prevention, treatment and cure of this disease. This study aimed to evaluate the in vitro activity of new imidazolidine compounds 1-benzyl-4-[(4-chloro-phenyl)-hydrazono]-5-thioxo-imidazolidin-2-one (LPSF/PT-5) and 1-(4-chloro-benzyl)-4-[(4-fluoro-phenyl)-hydrazono]-5-thioxo-imidazolidin-2-one (LPSF/PT-11) against adult worms of S. mansoni. LPSF/PT-5 and LPSF/PT-11 imidazolidine derivatives showed relevant schistosomicidal activity in vitro and induced significant ultrastructural alterations in worms and cell death: results similar to praziquantel. Thus, it is possible that these imidazolidine derivatives can be future candidates as schistosomotic drugs, but further studies are needed to elucidate the induced mechanisms behind this response.

摘要

血吸虫病是一种由血吸虫属的寄生虫引起的疾病,它威胁着全球约 2.07 亿人。最近,曼氏血吸虫的菌株似乎对吡喹酮产生了耐受性和耐药性,吡喹酮是市场上最常用的治疗这种疾病的药物。这种令人担忧的发展情况证明了研究替代药物预防、治疗和治愈这种疾病的合理性。本研究旨在评估新型咪唑烷化合物 1-苄基-4-[(4-氯-苯基)-腙基]-5-硫代-咪唑烷-2-酮 (LPSF/PT-5) 和 1-(4-氯-苄基)-4-[(4-氟-苯基)-腙基]-5-硫代-咪唑烷-2-酮 (LPSF/PT-11) 对曼氏血吸虫成虫的体外活性。LPSF/PT-5 和 LPSF/PT-11 咪唑烷衍生物在体外表现出相关的杀血吸虫活性,并诱导蠕虫和细胞死亡发生显著的超微结构改变:与吡喹酮的结果相似。因此,这些咪唑烷衍生物有可能成为未来的抗血吸虫药物候选物,但需要进一步的研究来阐明这种反应背后的诱导机制。

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