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用于血吸虫病的药物重新利用:药物或生物分子的组合

Drug Repurposing for Schistosomiasis: Combinations of Drugs or Biomolecules.

作者信息

Gouveia Maria João, Brindley Paul J, Gärtner Fátima, Costa José M Correia da, Vale Nuno

机构信息

UCBIO/REQUIMTE, Laboratory of Pharmacology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo, 228, 4050-313 Porto, Portugal.

Center for the Study of Animal Science, ICETA, University of Porto, Praça Gomes Teixeira, Apartado 55142, 4031-401 Porto, Portugal.

出版信息

Pharmaceuticals (Basel). 2018 Feb 5;11(1):15. doi: 10.3390/ph11010015.

Abstract

Schistosomiasis is a major neglected tropical disease. Control of schistosomiasis currently relies on a single drug, praziquantel, and despite its efficacy against the all schistosome species that parasitize humans, it displays some problematic drawbacks and alone is ineffective in counteracting adverse pathologies associated with infection. Moreover, due to the development of the potential emergence of PZQ-resistant strains, the search for additional or alternative antischistosomal drugs have become a public health priority. The current drug discovery for schistosomiasis has been slow and uninspiring. By contrast, repurposing of existing approved drugs may offer a safe, rapid and cost-effective alternative. Combined treatment with PZQ and other drugs with different mode of action, i.e., antimalarials, shows promise results. In addition, a combination of anthelminthic drugs with antioxidant might be advantageous for modulating oxidative processes associated with schistosomiasis. Herein, we review studies dealing with combination therapies that involve PZQ and other anthelminthic drugs and/or antioxidant agents in treatment of schistosomiasis. Whereas PZQ combined with antioxidant agents might or might not interfere with anthelminthic efficacy, combinations may nonetheless ameliorate tissue damage and infection-associated complications. In fact, alone or combine with other drugs, antioxidants might be a valuable adjuvant to reduce morbidity and mortality of schistosomiasis. Therefore, attempting new combinations of anthelmintic drugs with other biomolecules such as antioxidants provides new avenues for discovery of alternatives to PZQ.

摘要

血吸虫病是一种主要的被忽视热带病。目前,血吸虫病的防治依赖单一药物吡喹酮,尽管它对寄生于人体的所有血吸虫种类都有效,但仍存在一些问题和缺点,且单独使用对对抗与感染相关的不良病理状况无效。此外,由于可能出现吡喹酮耐药菌株,寻找其他或替代抗血吸虫药物已成为公共卫生的当务之急。目前针对血吸虫病的药物研发进展缓慢且成效不佳。相比之下,重新利用现有已批准药物可能提供一种安全、快速且具有成本效益的替代方案。吡喹酮与其他具有不同作用方式的药物(即抗疟药)联合治疗显示出有前景的结果。此外,驱虫药与抗氧化剂联合使用可能有利于调节与血吸虫病相关的氧化过程。在此,我们综述了涉及吡喹酮与其他驱虫药和/或抗氧化剂联合治疗血吸虫病的研究。虽然吡喹酮与抗氧化剂联合使用可能会或可能不会干扰驱虫效果,但联合使用仍可能改善组织损伤和与感染相关的并发症。事实上,单独使用或与其他药物联合使用时,抗氧化剂可能是降低血吸虫病发病率和死亡率的有价值辅助药物。因此,尝试将驱虫药与其他生物分子(如抗氧化剂)进行新的联合,为发现吡喹酮的替代药物提供了新途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd47/5874711/0d6974eab2c7/pharmaceuticals-11-00015-g001.jpg

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