Toxoplasma gondii: In vitro and in vivo activities of the hydroxynaphthoquinone 2-hydroxy-3-(1′-propen-3-phenyl)-1,4-naphthoquinone alone or combined with sulfadiazine

Ferreira, Rondinele Alberto dos Reis; Oliveira, Alaı́de Braga de; Ribeiro, Múcio Flávio Barbosa; Tafuri, Wagner Luiz; Vítor, Ricardo Wagner Almeida

doi:10.1016/j.exppara.2005.12.006

Cited by 30 publications

(11 citation statements)

References 13 publications

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“…Since the vast majority of drugs currently used to treat toxoplasmosis in humans do not demonstrate such activity, eradication of the parasite from the host has not been achieved. Several groups have reported a reduction of cyst numbers in mouse models of acute or latent infection by use of, among others, the anticoccidial drug ponazuril (231,232), artemisinin derivates (233), and 2-hydroxy-3-(1-propen-3-phenyl)-1,4-naphthoquinone (PHNQ6) alone or combined with sulfadiazine (234). In an elegant series of in vitro and in vivo experiments, the endochin-like quinolone ELQ-316 demonstrated a favorable median effective dose (ED 50 ) compared to that of atovaquone when administered orally to acutely infected mice; furthermore, ELQ-316 at 25 mg/kg reduced the cyst burden significantly compared to that with atovaquone (88% versus 44% reduction) after 16 days of treatment, without showing overt toxicity in mice (235).…”

Section: Drugs For Treatment Of Acute T Gondii Infection In Mammalsmentioning

confidence: 99%

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

et al. 2018

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SUMMARYPrimary infection is usually subclinical, but cervical lymphadenopathy or ocular disease can be present in some patients. Active infection is characterized by tachyzoites, while tissue cysts characterize latent disease. Infection in the fetus and in immunocompromised patients can cause devastating disease. The combination of pyrimethamine and sulfadiazine (pyr-sulf), targeting the active stage of the infection, is the current gold standard for treating toxoplasmosis, but failure rates remain significant. Although other regimens are available, including pyrimethamine in combination with clindamycin, atovaquone, clarithromycin, or azithromycin or monotherapy with trimethoprim-sulfamethoxazole (TMP-SMX) or atovaquone, none have been found to be superior to pyr-sulf, and no regimen is active against the latent stage of the infection. Furthermore, the efficacy of these regimens against ocular disease remains uncertain. In multiple studies, systematic screening for infection during gestation, followed by treatment with spiramycin for acute maternal infections and with pyr-sulf for those with established fetal infection, has been shown to be effective at preventing vertical transmission and minimizing the severity of congenital toxoplasmosis (CT). Despite significant progress in treating human disease, there is a strong impetus to develop novel therapeutics for both the acute and latent forms of the infection. Here we present an overview of toxoplasmosis treatment in humans and in animal models. Additional research is needed to identify novel drugs by use of innovative high-throughput screening technologies and to improve experimental models to reflect human disease. Such advances will pave the way for lead candidates to be tested in thoroughly designed clinical trials in defined patient populations.

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Section: Drugs For Treatment Of Acute T Gondii Infection In Mammalsmentioning

confidence: 99%

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

et al. 2018

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“…Possible substitute drugs for sulfadiazine include dapsone (diaminodiphenyl sulfone), clindamycin, spiramycin, or clarithromycin. The agent hydroxynaphthoquinone is thought to be effective against bradyzoite-containing cysts and has provided prolonged remission of toxoplasmosis in an rodent experimental model (Ferreira et al, 2006). A white-throated capuchin monkey with neurological signs was successfully treated with clindamycin and trimethaprim-sulfamethoxazole, which resulted in improvement within three days and complete clinical resolution within two weeks (Fiorella et al, 2006).…”

Section: Protozoan Diseases Toxoplasmosismentioning

confidence: 99%

Respiratory System Diseases of Nonhuman Primates

Lowenstine

Osborn

2012

Nonhuman Primates in Biomedical Research

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“…The compound 2-hydroxy-3-(1′-propen-3-phenyl)-1, 4-naphthoquinone (PHNQ6), (50 mg/kg/day) combined with sulfadiazine showed reduction or elimination of brain cysts in vivo (Ferreira et al, 2006). In another study that coadministered spiramycin and metronidazole, spiramycin, did not reach effective concentrations in the brain due to the presence of the efflux transporters multidrug-resistant protein 2, and P-glycoprotein.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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.

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Toxoplasma gondii: In vitro and in vivo activities of the hydroxynaphthoquinone 2-hydroxy-3-(1′-propen-3-phenyl)-1,4-naphthoquinone alone or combined with sulfadiazine

Cited by 30 publications

References 13 publications

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

Respiratory System Diseases of Nonhuman Primates

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

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