Montazeri Mahbobeh, Sharif Mehdi, Sarvi Shahabeddin, Mehrzadi Saeed, Ahmadpour Ehsan, Daryani Ahmad
Toxoplasmosis Research Center, Mazandaran University of Medical SciencesSari, Iran; Student Research Committee, Mazandaran University of Medical SciencesSari, Iran.
Toxoplasmosis Research Center, Mazandaran University of Medical SciencesSari, Iran; Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical SciencesSari, Iran.
Front Microbiol. 2017 Jan 20;8:25. doi: 10.3389/fmicb.2017.00025. eCollection 2017.
The currently available anti- agents have serious limitations. This systematic review was performed to evaluate drugs and new compounds used for the treatment of toxoplasmosis. Data was systematically collected from published papers on the efficacy of drugs/compounds used against () globally during 2006-2016. The searched databases were PubMed, Google Scholar, Science Direct, ISI Web of Science, EBSCO, and Scopus. One hundred and eighteen papers were eligible for inclusion in this systematic review, which were both and studies. Within this review, 80 clinically available drugs and a large number of new compounds with more than 39 mechanisms of action were evaluated. Interestingly, many of the drugs/compounds evaluated against act on the apicoplast. Therefore, the apicoplast represents as a potential drug target for new chemotherapy. Based on the current findings, 49 drugs/compounds demonstrated half-maximal inhibitory concentration (IC) values of below 1 μM, but most of them were not evaluated further for effectiveness. However, the derivatives of the ciprofloxacin, endochin-like quinolones and 1-[4-(4-nitrophenoxy) phenyl] propane-1-one (NPPP) were significantly active against tachyzoites both and . Thus, these compounds are promising candidates for future studies. Also, compound 32 ( calcium-dependent protein kinase 1 inhibitor), endochin-like quinolones, miltefosine, rolipram abolish, and guanabenz can be repurposed into an effective anti-parasitic with a unique ability to reduce brain tissue cysts (88.7, 88, 78, 74, and 69%, respectively). Additionally, no promising drugs are available for congenital toxoplasmosis. In conclusion, as current chemotherapy against toxoplasmosis is still not satisfactory, development of well-tolerated and safe specific immunoprophylaxis in relaxing the need of dependence on chemotherapeutics is a highly valuable goal for global disease control. However, with the increasing number of high-risk individuals, and absence of a proper vaccine, continued efforts are necessary for the development of novel treatment options against . Some of the novel compounds reviewed here may represent good starting points for the discovery of effective new drugs. In further, bioinformatic and studies are needed in order to identify new potential toxoplasmicidal drugs.
目前可用的抗寄生虫药物存在严重局限性。本系统评价旨在评估用于治疗弓形虫病的药物和新化合物。系统收集了2006年至2016年期间全球发表的关于药物/化合物抗弓形虫疗效的论文数据。检索的数据库包括PubMed、谷歌学术、科学Direct、ISI科学网、EBSCO和Scopus。118篇论文符合纳入本系统评价的标准，均为临床研究和实验研究。在本评价中，评估了80种临床可用药物和大量具有39种以上作用机制的新化合物。有趣的是，许多评估的抗弓形虫药物/化合物作用于顶质体。因此，顶质体是新化疗潜在的药物靶点。根据目前的研究结果，49种药物/化合物的半数最大抑制浓度（IC）值低于1μM，但其中大多数未进一步评估其有效性。然而，环丙沙星衍生物、类内二喹啉和1-[4-(4-硝基苯氧基)苯基]丙烷-1-酮（NPPP）在体内和体外对弓形虫速殖子均具有显著活性。因此，这些化合物是未来研究的有希望的候选药物。此外，化合物32（钙依赖性蛋白激酶1抑制剂）、类内二喹啉、米替福新、咯利普兰和胍那苄可重新用作有效的抗寄生虫药物，具有减少脑组织囊肿的独特能力（分别为88.7%、88%、78%、74%和69%）。此外，目前尚无治疗先天性弓形虫病的有效药物。总之，由于目前针对弓形虫病的化疗仍不尽人意，开发耐受性良好且安全的特异性免疫预防措施以减少对化疗的依赖需求，是全球疾病控制的一个极具价值的目标。然而，随着高危人群数量的增加以及缺乏合适的疫苗，仍需继续努力开发针对弓形虫病的新治疗方案。这里综述的一些新化合物可能是发现有效新药的良好起点。此外，需要进行生物信息学和实验研究以确定新的潜在抗弓形虫药物。
