Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets.
Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets.
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DOI：
10.1016/j.cbpb.2017.07.001
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
El Kouni MH
中科院分区：
文献类型：
--
作者：
El Kouni MH
血吸虫是寄生虫病血吸虫病的罪魁祸首，血吸虫病是一种急性和慢性寄生虫病，影响着全世界70个国家的2.4亿多人。它是仅次于疟疾的第二大毁灭性寄生虫病。每年至少有20万人死于这种疾病。在没有疫苗的情况下，化疗是防治血吸虫病的主要手段。目前，抗溶酶体药物库仅限于一种药物吡喹酮，这种药物在一天的治疗中非常有效，几乎没有宿主毒性。然而，最近有人提出了吡喹酮活性降低的问题。因此，寻找替代的抗肿瘤药物值得研究新的化疗方法。药物的合理设计通常基于病原体和宿主之间的生化和生理差异。嘧啶代谢是此类研究的绝佳目标。与大多数宿主组织不同，血吸虫需要非常活跃的嘧啶代谢来合成DNA和RNA。这对于寄生虫每天产生大量虫卵是必不可少的，肉芽肿反应促使血吸虫病的发病。此外，在宿主和寄生虫的嘧啶代谢的相应酶之间存在足够的差异，可以利用这些差异来设计寄生酶的特异性抑制剂或“破坏性底物”。嘧啶转运的特异性在寄生虫和哺乳动物宿主之间也有显著差异。本文综述了嘧啶代谢的研究，并强调了这种代谢的独特性，可能构成良好的潜在目标，设计安全，有效的抗嘧啶药物。此外，嘧啶代谢的mesosomes相比，在其他寄生虫的嘧啶代谢的研究已经更详细，希望提供线索，如何确定可能的化疗靶点，还没有在mesosomes。
Schistosomes are responsible for the parasitic disease schistosomiasis, an acute and chronic parasitic ailment that affects more than 240 million people in 70 countries worldwide. It is the second most devastating parasitic disease after malaria. At least 200,000 deaths per year are associated with the disease. In the absence of the availability of vaccines, chemotherapy is the main stay for combating schistosomiasis. The antischistosomal arsenal is currently limited to a single drug, Praziquantel, which is quite effective with a single-day treatment and virtually no host-toxicity. Recently, however, the question of reduced activity of Praziquantel has been raised. Therefore, the search for alternative antischistosomal drugs merits the study of new approaches of chemotherapy. The rational design of a drug is usually based on biochemical and physiological differences between pathogens and host. Pyrimidine metabolism is an excellent target for such studies. Schistosomes, unlike most of the host tissues, require a very active pyrimidine metabolism for the synthesis of DNA and RNA. This is essential for the production of the enormous numbers of eggs deposited daily by the parasite to which the granulomas response precipitate the pathogenesis of schistosomiasis. Furthermore, there are sufficient differences between corresponding enzymes of pyrimidine metabolism from the host and the parasite that can be exploited to design specific inhibitors or “subversive substrates” for the parasitic enzymes. Specificities of pyrimidine transport also diverge significantly between parasites and their mammalian host. This review deals with studies on pyrimidine metabolism in schistosomes and highlights the unique characteristic of this metabolism that could constitute excellent potential targets for the design of safe and effective antischistosomal drugs. In addition, pyrimidine metabolism in schistosomes is compared with that in other parasites where studies on pyrimidine metabolism have been more elaborate, in the hope of providing leads on how to identify likely chemotherapeutic targets which have not been looked at in schistosomes.
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影响因子：
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作者：
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DOI：
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