Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

Porto, Raquel; Mengarda, Ana C.; Cajas, Rayssa A.; Salvadori, M. C.; Teixeira, F. S.; Arcanjo, Daniel Dias Rufino; Siyadatpanah, Abolghasem; Pereira, Maria de Lourdes; Wilairatana, Polrat; Moraes, Josué de

doi:10.3390/ph14070686

Cited by 21 publications

(17 citation statements)

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“…Adult schistosomes (BH strain) were isolated from infected mice and cultured in RPMI medium + 10% fetal calf serum and 100 U/mL penicillin and 100 μg/mL streptomycin in a 24-well culture plate (Corning, New York, NY, USA) containing one pair of parasites per well at 37 °C and 5% CO 2 (Panasonic Healthcare, Sakata, Oizumi-machi, Japan) 38 , 39 . For antischistosomal assay, compounds were dissolved in DMSO (final concentration of 0.5% v/v).…”

Section: Methodsmentioning

confidence: 99%

Pyrazoline derivatives as promising novel antischistosomal agents

Morais

Mengarda

Miguel

et al. 2021

Sci Rep

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Praziquantel is the only available drug to treat schistosomiasis, a parasitic disease that currently infects more than 240 million people globally. Due to increasing concerns about resistance and inadequate efficacy there is a need for new therapeutics. In this study, a series of 17 pyrazolines (15–31) and three pyrazoles (32–34) were synthesized and evaluated for their antiparasitic properties against ex vivo adult Schistosoma mansoni worms. Of the 20 compounds tested, six had a 50% effective concentration (EC50) below 30 μM. Our best hit, pyrazoline 22, showed promising activity against adult schistosomes, with an EC50 < 10 µM. Additionally, compound 22 had low cytotoxicity, with selectivity index of 21.6 and 32.2 for monkey and human cell lines, respectively. All active pyrazolines demonstrated a negative effect on schistosome fecundity, with a marked reduction in the number of eggs. Structure–activity relationship analysis showed that the presence of the non-aromatic heterocycle and N-substitution are fundamental to the antischistosomal properties. Pharmacokinetics, drug-likeness and medicinal chemistry friendliness studies were performed, and predicted values demonstrated an excellent drug-likeness profile for pyrazolines as well as an adherence to major pharmaceutical companies’ filters. Collectively, this study demonstrates that pyrazoline derivatives are promising scaffolds in the discovery of novel antischistosomal agents.

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Section: Methodsmentioning

confidence: 99%

Pyrazoline derivatives as promising novel antischistosomal agents

Morais

Mengarda

Miguel

et al. 2021

Sci Rep

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“…Understanding that these processes have important roles in reperfusion injury after myocardial infarction led to the evaluation of hydralazine for the treatment of myocardial injury after infarction, with promising results in in vivo models 18 . Other cardiovascular drugs that have been studied as therapies for other diseases include diuretics as antiparasitic agents (tested in vitro) 19 , statins as adjuvant therapy for cancers (reviewed previously 20 ) and antihypertensive agents for bipolar disorder 21 .…”

Section: Observation-driven Drug Repurposingmentioning

confidence: 99%

Repurposing drugs to treat cardiovascular disease in the era of precision medicine

et al. 2022

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Drug repurposing is the use of a given therapeutic agent for indications other than that for which it was originally designed or intended. The concept is appealing because of potentially lower development costs and shorter timelines than are needed to produce a new drug. To date, drug repurposing for cardiovascular indications has been opportunistic and driven by knowledge of disease mechanisms or serendipitous observation rather than by systematic endeavours to match an existing drug to a new indication. Innovations in two areas of personalized medicine — computational approaches to associate drug effects with disease signatures and predictive model systems to screen drugs for disease-modifying activities — support efforts that together create an efficient pipeline to systematically repurpose drugs to treat cardiovascular disease. Furthermore, new experimental strategies that guide the medicinal chemistry re-engineering of drugs could improve repurposing efforts by tailoring a medicine to its new indication. In this Review, we summarize the historical approach to repurposing and discuss the technological advances that have created a new landscape of opportunities.

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“…Schistosomiasis, caused by helminth parasites of the genus Schistosoma , is a neglected tropical disease with an estimated global prevalence of 240 million infected people in 78 countries and significant mortality and social and economic consequences [ 1 , 2 , 3 ]. Praziquantel (PZQ) is the only drug currently available for the treatment of all Schistosoma species [ 2 , 3 , 4 , 5 ], including Schistosoma mansoni , which is the species prevalent in South America, the Middle East, and Africa [ 1 , 3 , 6 ]. However, despite its effectiveness, PZQ has no efficacy against juvenile worms, which is a limit to schistosomiasis control and elimination [ 1 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, despite its effectiveness, PZQ has no efficacy against juvenile worms, which is a limit to schistosomiasis control and elimination [ 1 , 4 , 5 ]. Additionally, the emerging PZQ-resistance and its reduced efficacy after use over the last decades have also been reported [ 1 , 2 , 3 ]. Therefore, the need for identification of new therapeutic targets and antischistosomal drugs is crucial.…”

Section: Introductionmentioning

confidence: 99%

“…In this regard, S. mansoni NTPDases (known as ATP diphosphohydrolases, ecto-apyrases or SmNTPDases) have gained interest as potential drug target for discovering of new antischistosomal drugs [ 1 , 2 , 3 , 7 , 8 ]. It has been suggested that SmNTPDases inhibitors might act in Schistosoma due to several possible mechanisms, such as reducing the parasite’s survival and improving the host’s immune response [ 1 , 2 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Identification of Asiaticoside from Centella erecta (Apiaceae) as Potential Apyrase Inhibitor by UF-UHPLC-MS and Its In Vivo Antischistosomal Activity

et al. 2022

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Schistosomiasis, caused by parasites of the genus Schistosoma, is a neglected disease with high global prevalence, affecting more than 240 million people in several countries. Praziquantel (PZQ) is the only drug currently available for the treatment. S. mansoni NTPDases (known as SmNTPDases, ATP diphosphohydrolases or ecto-apyrases) are potential drug targets for the discovery of new antischistosomal drugs. In this study, we screen NTPDases inhibitors from Centella erecta (Apiaceae) using an ultrafiltration combined UHPLC-QTOF-MS method and potato apyrase, identifying asiaticoside as one of the apyrase-binding compounds. After isolation of asiaticoside from C. erecta extract, we assessed its in vivo antischistosomal activities against Schistosoma mansoni worms and its in vitro enzymatic apyrase inhibition. Also, molecular docking analysis of asiaticoside against potato apyrase, S. mansoni NTPDases 1 and 2 were performed. Asiaticoside showed a significant in vitro apyrase inhibition and molecular docking studies corroborate with its possible actions in potato apyrase and S. mansoni NTPDases. In mice harboring a patent S. mansoni infection, a single oral dose of asiaticoside (400 mg/kg. p.o.) showed significantly in vivo antischistosomal efficacy, markedly decreasing the total worm load and egg burden, giving support for further exploration of apyrase inhibitors as antischistosomal agents.

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Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

Cited by 21 publications

References 50 publications

Pyrazoline derivatives as promising novel antischistosomal agents

Pyrazoline derivatives as promising novel antischistosomal agents

Repurposing drugs to treat cardiovascular disease in the era of precision medicine

Identification of Asiaticoside from Centella erecta (Apiaceae) as Potential Apyrase Inhibitor by UF-UHPLC-MS and Its In Vivo Antischistosomal Activity

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