A Systematic Review ofIn vitroandIn vivoActivities of Anti-ToxoplasmaDrugs and Compounds (2006-2016).
The currently available anti-Toxoplasmaagents 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 againstToxoplasma gondii(T. gondii) 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 bothin vitroandin vivostudies. 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 againstT. gondiiact on the apicoplast. Therefore, the apicoplast represents as a potential drug target for new chemotherapy. Based on the current findings, 49 drugs/compounds demonstratedin vitrohalf-maximal inhibitory concentration (IC50) values of below 1 μM, but most of them were not evaluated further forin vivoeffectiveness. However, the derivatives of the ciprofloxacin, endochin-like quinolones and 1-[4-(4-nitrophenoxy) phenyl] propane-1-one (NPPP) were significantly active againstT. gondiitachyzoites bothin vitroandin vivo. Thus, these compounds are promising candidates for future studies. Also, compound 32 (T. gondiicalcium-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 againstT. gondii. Some of the novel compounds reviewed here may represent good starting points for the discovery of effective new drugs. In further, bioinformatic andin silicostudies are needed in order to identify new potential toxoplasmicidal drugs.
Toxoplasmosis Research Center, Mazandaran University of Medical SciencesSari, Iran; Student Research Committee, Mazandaran University of Medical SciencesSari, Iran.
Mahbobeh
M
Montazeri
Toxoplasmosis Research Center, Mazandaran University of Medical SciencesSari, Iran; Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical SciencesSari, Iran.
Mehdi
M
Sharif
Toxoplasmosis Research Center, Mazandaran University of Medical SciencesSari, Iran; Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical SciencesSari, Iran.
Shahabeddin
S
Sarvi
Department of Pharmacology, School of Medicine, Iran University of Medical Sciences Tehran Iran.
Saeed
S
Mehrzadi
Drug Applied Research Center, Tabriz University of Medical Sciences Tabriz, Iran.
Ehsan
E
Ahmadpour
Toxoplasmosis Research Center, Mazandaran University of Medical SciencesSari, Iran; Department of Parasitology and Mycology, Sari Medical School, Mazandaran University of Medical SciencesSari, Iran.
Ahmad
A
Daryani
Toxoplasma gondii; compounds; drugs; in vitro; in vivo; toxoplasmosis