Sesquiterpenes evaluation on Schistosoma mansoni : Survival, excretory system and membrane integrity

Oliveira, Rosimeire Nunes de; Rodrigues-dos-Santos, Karina; Mendes, Tiago Manuel Fernandes; Garcia, Vera Lúcia; Oliveira, Adriana Silva Santos; Jeraldo, Verónica de Lourdes Sierpe; Allegretti, Silmara Marques

doi:10.1016/j.biopha.2017.04.058

Cited by 12 publications

(5 citation statements)

References 37 publications

(43 reference statements)

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“…Extending these assays to adult schistosome (7 wk old) mixed-sex cultures revealed a greater triterpenoid-mediated effect on male (EC 50 = 7.4 μM) compared to female (EC 50 = 10.3 μM) parasites. Although this gender biased (male > female) effect has been observed before for other (di- and sesqui-) terpenes/terpenoids ( Edwards et al, 2015 ; de Oliveira et al, 2017 ), this is not always seen ( de Moraes et al, 2014 ) and is most likely related to structural differences amongst this diverse class of compounds ( de Moraes, 2015 ; Mafud et al, 2016 ). Interestingly, egg production was also significantly inhibited in mixed-sex adult worm cultures even at concentrations of 700015 below the EC 50 s (5 μM - 2.5 μM) calculated for this lifecycle stage ( Fig.…”

Section: Resultsmentioning

confidence: 59%

“…Previous studies have demonstrated that the anthelmintic activity observed for mono-, di- and sesqui-terpenes/terpenoids is correlated to surface damage of both F. hepatica and S. mansoni ( Keiser and Utzinger, 2007 ; Keiser and Morson, 2008 ; de Moraes et al, 2013 ; Moraes et al, 2013 ; Edwards et al, 2015 ; de Oliveira et al, 2017 ; Crusco et al, 2018 ). Therefore, we next investigated whether tegumental surface membranes of both liver and blood flukes were negatively affected by sub-lethal concentrations (13.3 μM for F. hepatica adults, 10 μM for S. mansoni adults) of 700015 ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni

Whiteland

Chakroborty

Forde-Thomas

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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Two economically and biomedically important platyhelminth species, Fasciola hepatica (liver fluke) and Schistosoma mansoni (blood fluke), are responsible for the neglected tropical diseases (NTDs) fasciolosis and schistosomiasis. Due to the absence of prophylactic vaccines, these NTDs are principally managed by the single class chemotherapies triclabendazole (F. hepatica) and praziquantel (S. mansoni). Unfortunately, liver fluke resistance to triclabendazole has been widely reported and blood fluke insensitivity/resistance to praziquantel has been observed in both laboratory settings as well as in endemic communities. Therefore, the identification of new anthelmintics is necessary for the sustainable control of these NTDs in both animal and human populations. Here, continuing our work with phytochemicals, we isolated ten triterpenoids from the mature bark of Abies species and assessed their anthelmintic activities against F. hepatica and S. mansoni larval and adult lifecycle stages. Full 1H and 13C NMR-mediated structural elucidation of the two most active triterpenoids revealed that a tetracyclic steroid-like nucleus core and a lactone side chain are associated with the observed anthelmintic effects. When compared to representative mammalian cell lines (MDBK and HepG2), the most potent triterpenoid (700015; anthelmintic EC50s range from 0.7 μM–15.6 μM) displayed anthelmintic selectivity (selectivity indices for F. hepatica: 13 for newly excysted juveniles, 46 for immature flukes, 2 for mature flukes; selectivity indices for S. mansoni: 14 for schistosomula, 9 for immature flukes, 4 for adult males and 3 for adult females) and induced severe disruption of surface membranes in both liver and blood flukes. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also severely inhibited by 700015. Together, our results describe the structural elucidation of a novel broad acting anthelmintic triterpenoid and support further investigations developing this compound into more potent analogues for the control of both fasciolosis and schistosomiasis.

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Section: Resultsmentioning

confidence: 59%

Section: Resultsmentioning

confidence: 99%

An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni

Whiteland

Chakroborty

Forde-Thomas

et al. 2018

International Journal for Parasitology: Drugs and Drug Resistan

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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%

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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“…A previous study [ 31 ] reported the observation of physiological and morphological changes, apart from the lethal effect on the studied organism, by in vitro screening of chemical substances. Our findings revealed that all three eugenol derivatives caused mortality of the worms in a dose- and time-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in silico evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools

Souza

Novaes

Gonçalves

et al. 2022

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Eugenol shows both antibacterial and antiparasitic activities, suggesting that it might be evaluated as an option for the treatment of praziquantel-resistant schistosome. Methods: The in vitro activities of three eugenol derivatives (FB1, FB4 and FB9) on adult worms from Schistosoma mansoni were examined by fluorescence and scanning electron microscopy to analyze effects on the excretory system and integument damage, respectively. Biochemical tests with verapamil (a calcium channel antagonist) and ouabain (a Na + /K + -ATPase pump inhibitor) were used to characterize eugenol derivative interactions with calcium channels and the Na + /K + -ATPase, while in silico analysis identified potential Na + /K + -ATPase binding sites. Results: The compounds showed effective doses (ED 50 ) of 0.324 mM (FB1), 0.167 mM (FB4), and 0.340 mM (FB9). In addition, FB4 (0.322 mM), which showed the lowest ED 50, ED 90 and ED 100 (p < 0.05), caused the most damage to the excretory system and integument, according to both fluorescence and scanning electron microscopy analysis. The death of adult worms was delayed by ouabain treatment plus FB1 (192 versus 72 hours) and FB9 (192 versus 168 hours), but the response to FB4 was the same in the presence or absence of ouabain. Besides, no changes were noted when all of the eugenol derivatives were combined with verapamil. Moreover, FB1 and FB9 inhibited

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Sesquiterpenes evaluation on Schistosoma mansoni : Survival, excretory system and membrane integrity

Cited by 12 publications

References 37 publications

An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni

An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni

Synthetic Aurones: New Features forSchistosoma mansoniTherapy

In vitro and in silico evaluation of the schistosomicidal activity of eugenol derivatives using biochemical, molecular, and morphological tools

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