In vitro and in vivo activities of multi-target phtalimido-thiazoles on Schistosomiasis mansoni

Filho, Carlos André Laranjeira Miranda; Barbosa, Míria de Oliveira; Oliveira, Arsênio Rodrigues; Santiago, Edna Farias; Souza, Veruska Cíntia Alexandrino de; Lucena, Jéssica Paula; Fernandes, Camila Juliet Barbosa; Santos, Ignes Regina Dos; Leão, Renata Lins Carneiro; Santos, Fábio André Brayner dos; Alves, Luíz Carlos; Pereira, Valéria Rêgo Alves; Araújo, Roni E.; Leite, Ana Cristina Lima; Oliveira, Sheilla Andrade de

doi:10.1016/j.ejps.2020.105236

Cited by 5 publications

(3 citation statements)

References 29 publications

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“…The discovery of new antischistosomal compounds is crucial in terms of public health, since schistosomiasis remains as the second most important human parasitic disease [ 1 , 4 , 41 ]. Due to the imperative need to identify new drugs, several natural compounds have been recently studied against S. mansoni [ 1 , 6 ].…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…In addition, it is considered to be a major target for antischistosomal drugs [ 38 ]. Alterations of the tegument can also be used to evaluate the antischistosomal activity of a compound [ 39 ]. Campelo et al [ 17 ] observed extensive soft tissue damage on the surface of S. mansoni exposed to combinations of piplartine, epiisopiloturine, and PZQ, and they demonstrated synergistic effects of compound combinations by ultrastructural study.…”

Section: Discussionmentioning

confidence: 99%

Synergistic effect of combination chemotherapy with praziquantel and DW-3-15 for Schistosoma japonicum in vitro and in vivo

et al. 2021

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Background Schistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease. In our previous studies, we found that the patented compound DW-3-15 (patent no. ZL201110142538.2) displayed significant and stabilized antiparasitic activity through a mechanism that might be distinct from PZQ. Here, we investigated the antischistosomal efficacy of PZQ combined with DW-3-15 against schistosomula and adult worms of Schistosoma japonicum in vitro and in vivo, to verify whether there was a synergistic effect of the two compounds. Methods The antischistosomal efficacy of PZQ combined with DW-3-15 in comparison with an untreated control and monotherapy group against schistosomula and adult worms was assessed both in vitro and in vivo. Parasitological studies, scanning electron microscopy, combination index, and histopathological analysis were used for the assessment. Results The results showed significantly reduced viability of schistosomes, achieving 100% viability reduction for juveniles and males by combination chemotherapy using PZQ together with DW-3-15 in vitro. The combination index was 0.28, 0.27, and 0.53 at the higher concentration of PZQ combined with DW-3-15 against juveniles, males, and females, respectively, indicating that the two compounds display strong synergism. Scanning electron microscopy observations also demonstrated that the compound combination induced more severe and extensive alterations to the tegument and subtegument of S. japonicum than those with each compound alone. In vivo, compared with the single-compound-treated group, the group treated with the higher-dose combination demonstrated the best schistosomicidal efficacy, with significantly reduced worm burden, egg burden, and granuloma count and area, which was evident against schistosomula and adult worms. Conclusions Our study provides a potential novel chemotherapy for schistosomiasis caused by S. japonicum. It would improve the antischistosomal effect on schistosomula and adult worms of S. japonicum, and decrease individual dosages. Graphical Abstract

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“…Disruption to the integument of the parasite exposes the worms to the immune system of the host and thus interferes with their survival. 44 Many schistosomulum medications currently in use, such as PZQ, 45 mefloquine, 46 and artemether, 47 cause damage to the schistosomal integument.…”

Section: Discussionmentioning

confidence: 99%

Cucurbita pepo Seed Oil Induces Microsatellite Instability and Tegumental Damage to Schistosoma mansoni Immature and Adult Worms In vitro

Ammar

Afifi

Essa

et al. 2020

IDR

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Background: Schistosomiasis is a tropical parasitic disease treated exclusively with praziquantel (PZQ). However, PZQ has low efficacy against schistosomula and juveniles. In addition, the emergence of PZQ resistance has prompted the search for new drugs. Methods: This study investigated the effects of pumpkin (Cucurbita pepo)-seed oil (PSO) on Schistosoma mansoni adults, juveniles, and newly formed schistosomula in vitro by exposing the parasites to increasing concentrations of PSO (20, 40, 60, 80, and 100 µl/ mL) with variable incubation periods (24, 48, and 72 hours). Dose-response effects of PSO on mortality rate, worm activity, and tegumental changes were studied. Also, effect on DNA were assessed with microsatellite analysis. Results: All tested stages of S. mansoni were susceptible to PSO, which was more effective than PZQ on juvenile worms and schistosomula. Juveniles and schistosomula S. mansoni were more sensitive to the antischistosomal activity of PSO than adult worms. PSO showed evident changes in the integuments of adults, juveniles, and schistosomula. These changes were more evident with increased concentrations. At the genomic level, PSO induced clear qualitative and quantitative changes in the microsatellite loci R95529 and SMD57 of S. mansoni adults and schistosomula. This microsatellite instability is being reported through the current study for S. mansoni in response to PSO for the first time. Conclusion: This study suggested that PSO possesses effective antischistosomal activity against various stages of S. mansoni. Further investigations are needed to figure out the mechanism of action of PSO on this parasite.

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In vitro and in vivo activities of multi-target phtalimido-thiazoles on Schistosomiasis mansoni

Cited by 5 publications

References 29 publications

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

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

Synergistic effect of combination chemotherapy with praziquantel and DW-3-15 for Schistosoma japonicum in vitro and in vivo

<p><em>Cucurbita pepo</em> Seed Oil Induces Microsatellite Instability and Tegumental Damage to <em>Schistosoma mansoni</em> Immature and Adult Worms In vitro</p>

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