Drugs in development for toxoplasmosis: advances, challenges, and current status.
Drugs in development for toxoplasmosis: advances, challenges, and current status.
复制标题
弓形虫病发育中的药物：进步，挑战和当前状态。
DOI：
10.2147/dddt.s60973
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Doggett JS
中科院分区：
文献类型：
--
作者：
Alday PH;Doggett JS
刚地弓形虫会引发致命且使人衰弱的脑部和眼部疾病。目前用于治疗弓形虫病的药物通常具有毒性副作用，且需要持续数周甚至一年以上的长期疗程。需要长时间治疗以及疾病有复发风险，部分原因是对刚地弓形虫组织包囊缺乏疗效。开发更有效治疗弓形虫病的挑战包括降低毒性、使药物在脑部和眼部达到治疗浓度、缩短疗程、从宿主体内清除组织包囊、在孕期使用安全，以及研制出一种在世界资源匮乏地区既便宜又实用的配方。在过去十年中，在识别和开发用于治疗弓形虫病的新化合物方面取得了重大进展。与临床上用于治疗弓形虫病的重新利用的药物不同，这些化合物在临床前开发过程中针对弓形虫病的疗效进行了优化。具有增强疗效以及针对弓形虫病独特方面特点的药物有可能极大地改善弓形虫病的治疗。这篇综述讨论了与药物设计相关的弓形虫病的各个方面，以及弓形虫病临床前药物研究的进展、挑战和现状。
Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis.