A Systematic Review of In vitro and In vivo Activities of Anti-Toxoplasma Drugs and Compounds (2006–2016)

Abstract

The currently available anti-Toxoplasma 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 Toxoplasma 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 both in vitro and in vivo 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 T. gondii 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 in vitro half-maximal inhibitory concentration (IC50) values of below 1 μM, but most of them were not evaluated further for in vivo effectiveness. However, the derivatives of the ciprofloxacin, endochin-like quinolones and 1-[4-(4-nitrophenoxy) phenyl] propane-1-one (NPPP) were significantly active against T. gondii tachyzoites both in vitro and in vivo. Thus, these compounds are promising candidates for future studies. Also, compound 32 (T. gondii 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 T. gondii. Some of the novel compounds reviewed here may represent good starting points for the discovery of effective new drugs. In further, bioinformatic and in silico studies are needed in order to identify new potential toxoplasmicidal drugs.

Transcriptional changes in Toxoplasma gondii in response to treatment with monensin

“…The search for new anti-Toxoplasma gondii drugs has been active for several decades [12,13], but only a few drugs are currently approved for use in humans [1,27]. Although sulfa drugs can be effectively used for the prevention and control of T. gondii infection in humans and animals, their side effects should not be ignored [28].…”

“…These drawbacks pose a major obstacle in conventional chemotherapy of toxoplasmosis in humans. To this end, efforts have been made to identify new and more effective medicines [12,13] and to understand the mechanism of action [14] and perturbation associated with the currently used drugs [15].…”

Research on the effect and mechanism of antimicrobial peptides HPRP‐A1/A2 work against Toxoplasma gondii infection

“…The clinical manifestations of Toxoplasma infection vary, especially in immunocompromised patients, while current therapeutics cannot satisfactorily treat patients. Thus, the search for an alternative, safe and effective drug or useful precursor is necessary …”

“…Thus, the search for an alternative, safe and effective drug or useful precursor is necessary. 36,37 Antimicrobial peptides are initially derived from a wide range of organisms, such as bacteria, plants and vertebrates. They are important in the host's innate immune defence system.…”

Anti-Toxoplasma Activities of Zea Mays and Eryngium Caucasicum Extracts, In Vitro and In Vivo

“…In addition, there is no effective vaccine for prevention of infection in human [8, 13, 14]. Accordingly, new drugs with lack of toxicity and teratogenicity, effective penetration in the placenta, and parasiticidal effect against the different stage of Toxoplasma particularly cystic form are critically needed [15]. There are increasing studies of therapeutic potential of natural or herbal products and medicinal plants are considered to be generally safe and have low toxicity compared to synthetic drugs [16].…”