Antischistosomal properties of aurone derivatives against juvenile and adult worms of Schistosoma mansoni

Pereira, Vinícius R. D.; Silveira, Lígia S. da; Mengarda, Ana C.; Júnior, Ismael J. Alves; Silva, Ohana Oliveira Zuza da; Miguel, Fábio Balbino; Silva, Marcos P.; Almeida, Ayla das Chagas; Torres, Daniel da Silva; Pinto, Priscila de Faria; Coimbra, Elaine Soares; Moraes, Josué de; Couri, Mara R.C.; Filho, Ademar Alves da Silva

doi:10.1016/j.actatropica.2020.105741

Cited by 21 publications

(33 citation statements)

References 51 publications

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“…The helminths integument is a dynamic region that maintains a direct relationship with the mammalian host. In a very peculiar way, S. mansoni has a high longevity in the host, reaching decades without suffering any type of damage within the parasitized organism, so this membrane (integument) must play an important role in protecting this worm against the immune system [21,22,24] . Concerning this, in the in vitro studies, the schistosomicidal activity must be affect by one or more parameters, such as motor activity, oviposition, tegumental changes, which may be measured qualitatively and quantitatively through microscopic analysis [25,26,27,28] …”

Section: Resultsmentioning

confidence: 99%

“…Aurones were synthesized by cyclization of chalcones. To a solution of mercuric acetate (2.61 mmol) dissolved in pyridine was added chalcone (2.61 mmol) and the mixture was stirred at 110 °C for 1–48 h. The reaction mixture was cooled and acidified with HCl (10 % aqueous solution) [16,21] . The solution was taken up in CH 2 Cl 2 and washed successively with water.…”

Section: Methodsmentioning

confidence: 99%

“…Tegumental alteration and quantification of the number of tubercles were performed for the active compounds ( 1 ) and ( 2 ) at 5, 10, 25, 50 and 100 μM concentrations using a confocal laser‐scanning microscope. After the established times or in the occurrence of death, the parasites were fixed in Formalin‐acetic‐alcohol solution (FAA) and analyzed under a confocal microscope (Laser Scanning Microscopy, LSM 510 META, Zeiss) at 488 nm (exciting) and 505 nm (emission) [7,21] . The number of tubercles was counted in 20,000 μm 2 of area calculated with the Zeiss LSM Image Browser software.…”

Section: Methodsmentioning

confidence: 99%

“…Cytotoxicity in macrophages was determined with the MTT assay, [21] using different concentrations (5, 10, 25, 50 and 100 μM) of the active chalcones using three independent experiments in duplicate. Peritoneal macrophages used in this study were obtained according to previous report [21] . The values of cytotoxicity concentration to reduce 50 % of viable macrophages (CC 50 ) were obtained using GraFit Version 5 software.…”

Section: Methodsmentioning

confidence: 99%

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Synthetic Aurones: New Features forSchistosoma mansoniTherapy

Torres

Oliveira

Silveira

et al. 2021

Chemistry & Biodiversity

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In this work, two synthetic aurones revealed moderate schistosomicidal potential in in vitro and in vivo assays. Aurones (1) and (2) promoted changes in tegument integrity and motor activity, leading to death of adult Schistosoma mansoni worms in in vitro assays. When administered orally (two doses of 50 mg/kg) in experimentally infected animals, synthetic aurones (1) and (2) promoted reductions of 56.20 % and 57.61 % of the parasite load and stimulated the displacement towards the liver of the remaining adult worms. The oogram analysis revealed that the treatment with both aurones interferes with the egg development kinetics in the intestinal tissue. Seeking an action target for compounds (1) and (2), the connection with NTPDases enzymes, recognized as important therapeutic targets for S. mansoni, was evaluated. Molecular docking studies have shown promising results. The dataset reveals the anthelmintic character of these compounds, which can be used in the development of new therapies for schistosomiasis.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Synthetic Aurones: New Features forSchistosoma mansoniTherapy

Torres

Oliveira

Silveira

et al. 2021

Chemistry & Biodiversity

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“…Given the importance of the schistosomes’ tegument as a target for drugs [ 18 , 19 , 20 ], we used scanning electron microcopy to examine the surface of worms exposed to amiodarone, telmisartan, and propafenone. We found that treatment with any of the three cardiovascular drugs significantly damaged the worm’s tegument, usually with disintegration of tubercles.…”

Section: Discussionmentioning

confidence: 99%

Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

et al. 2021

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The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC50) and 90% (EC90) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent.

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Evaluation of Gibbilimbol B, Isolated from Piper malacophyllum (Piperaceae), as an Antischistosomal Agent

Carnaúba

Mengarda

Rodrigues

et al. 2021

Chemistry & Biodiversity

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Infections caused by parasitic worms impose a considerable worldwide health burden. One of the most impactful is schistosomiasis, a disease caused by blood‐dwelling of the genus Schistosoma that affects more than 230 million people worldwide. Since praziquantel has also been extensively used to treat schistosomiasis and other parasitic flatworm infections, there is an urgent need to identify novel anthelmintic compounds, mainly from natural sources. In this study, the hexane extract from roots of Piper malacophyllum (Piperaceae) showed to be mainly composed for gibbilimbol B by HPLC/ESI‐HRMS. Based on this result, this compound was isolated by chromatographic steps and its structure was confirmed by NMR. In vitro bioassays showed that gibbilimbol B was more active than praziquantel against larval stage of S. mansoni, with effective concentrations of 50 % (EC50) and 90 % (EC90) values of 2.6 and 3.4 μM, respectively. Importantly, gibbilimbol B showed no cytotoxicity to mammalian cells at a concentration 190 times greater than the antiparasitic effect, giving support for the anthelmintic potential of gibbilimbol B as lead compound for novel antischistosomal agents.

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Antischistosomal properties of aurone derivatives against juvenile and adult worms of Schistosoma mansoni

Cited by 21 publications

References 51 publications

Synthetic Aurones: New Features forSchistosoma mansoniTherapy

Synthetic Aurones: New Features forSchistosoma mansoniTherapy

Antiparasitic Properties of Cardiovascular Agents against Human Intravascular Parasite Schistosoma mansoni

Evaluation of Gibbilimbol B, Isolated from Piper malacophyllum (Piperaceae), as an Antischistosomal Agent

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