Antischistosomal activity of aminoalkanethiols, aminoalkanethiosulfuric acids and the corresponding disulfides

Penido, Marcus Luiz de Oliveira; Coelho, Paulo Marcos Zech; Mello, Rodrigo Fernandes de; Piló‐Veloso, Dorila; Oliveira, Mônica Cristina; Kusel, J. R.; Nelson, David Lee

doi:10.1016/j.actatropica.2008.10.005

Cited by 25 publications

(13 citation statements)

References 38 publications

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“…S. mansoni males are often more susceptible than female worms in studies on resistance to oxamniquine [39] and in studies regarding the bioactivity of ginger extract [36]. In contrast, the results with other compounds, such as fatty aminoalkanethiosulfuric [34] and 2-[butylamino]-1-phenyl-1-ethanethiosulfuric acid [6], revealed higher survival rates for males than females. Notably, in vitro data obtained in this study demonstrated that the EEE, HF, EAF, and 7-epi exhibited greater activity against adult male S. mansoni worms.…”

Section: E F)mentioning

confidence: 87%

Potent Schistosomicidal Constituents from Garcinia brasiliensis

et al. 2015

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Praziquantel is the drug of choice for the treatment of schistosomiasis. However, several strains of Schistosoma mansoni are resistant to praziquantel, making it necessary to discover new drugs that might be used for its treatment. With this in mind, the properties of a schistosomicidal ethanolic extract of Garcinia brasiliensis Mart. epicarp, the fractions obtained by partitioning this extract, including the hexane fractions, ethyl acetate fraction, and the aqueous fraction, and the isolated compounds 7-epiclusianone, a major component from these fractions, and fukugetin were tested in vitro on adult worms of S. mansoni. Mortality, damage to membranes, and excretory system activity were observed at 100.0, 50.0, 75.0, and 14.0 µg/mL for the ethanolic extract of G. brasiliensis Mart. epicarp, its hexane fractions, the ethyl acetate fraction, and 7-epiclusianone, respectively. For 7-epiclusianone, these data were confirmed by fluorescent probe Hoechst 33 258 and resorufin. Additionally, the biocidal effect of 7-epiclusianone was even higher than the hexane fractions. Moreover, an inhibitory effect of 7-epiclusianone on the egg laying of female adult S. mansoni worms was observed in cercariae and schistossomula. Thus, 7-epiclusianone is a promising schistosomicidal compound; however, more studies are needed to elucidate its mechanism of toxicity and to evaluate the in vivo activity of this compound.

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Section: E F)mentioning

confidence: 87%

Potent Schistosomicidal Constituents from Garcinia brasiliensis

et al. 2015

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“…Moreover, mefloquine was shown to exhibit a high capacity to induce morphological alteration in the outer membrane of schistosomula and adult schistosomes. Other examples of promising antischistosomal drugs under research include benzothiazole derivatives (Mahran et al 2007), aminoalkanethiols and corresponding disulfides (de Oliveira Penido et al 2008), alkoxyalkyl esters of acyclic nucleoside phosphonates (Botros et al 2009), trioxaquines (Boissier et al 2009), and thioxo-imidazoline compounds (Neves et al 2010(Neves et al , 2011. In addition, modifications in the manner of drug delivery for drugs with poor hydrosolubility have also been investigated to increase antischistosomal efficacy (de Araújo et al 2007).…”

Section: Discussionmentioning

confidence: 98%

Ultrastructural analysis of miltefosine-induced surface membrane damage in adult Schistosoma mansoni BH strain worms

et al. 2012

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Schistosomiasis is an infectious parasitic disease caused by helminths from the genus Schistosoma; it affects over 200 million people globally and is endemic in 70 countries. In Brazil, 6 million individuals are infected with Schistosoma mansoni. Furthermore, as the prevalence of S. mansoni infections is increasing, approximately 26 million citizens in 19 Brazilian states are at risk for infection. Schistosomiasis disease control involves predominately the administration of a single drug, praziquantel. Although praziquantel exhibits chemotherapeutic efficacy and safety, its massive use in endemic zones, the possibility of the emergence of drug-resistant Schistosoma parasites, and the lack of another efficacious antischistosomal drug demand the discovery of new schistosomicidal compounds. First developed as anti-tumor drug, miltefosine is an alkylphospholipid derivative that exhibits bioactivity against Leishmania and Trypanosoma parasites, free-living protozoa, bacteria, and fungi. With its anti-parasite activity, miltefosine was the first orally administered drug against visceral and cutaneous leishmaniasis approved. Previously, by means of the MTT cytotoxic assay and a DNA fragmentation test, we verified that, at doses of 100 and 200 μM (40 and 80 μg/mL), miltefosine exhibited in vitro schistosomicidal activity against adult S. mansoni worms. Here, we present ultrastructural evidence of rapid, severe miltefosine-induced surface membrane damage in S. mansoni following drug treatment. The number of dead parasites was concentration- and time-dependent following miltefosine treatment. At a miltefosine concentration of 200 μM (∼80 μg/mL), in vitro parasite killing was initiated as early as 3 h post-incubation, and it was maximal after 24 h of treatment. The parasite death was preceded by progressive surface membrane damage, characterized by tegument peeling, spine reduction and erosion, blister formation and rupture, and the emergence of holes. According to our present results, miltefosine is very effective at inducing membrane destruction of S. mansoni with a short onset of pharmacological action.

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“…Parameters, such as motor activity, eggs morphology, and tegumental changes, are often evaluated as indicators of biological activity in studies using schistosomes species (William et al, 2001 ; Sanderson et al, 2002 ; Pica-Mattoccia and Cioli, 2004 ; De Araújo et al, 2007 ; Xiao et al, 2007 ; de Oliveira Penido et al, 2008 ; Katz, 2008 ; Boissier et al, 2009 ; Magalhães et al, 2009 , 2010 ), hence we evaluate these parameters in order to assess the effect of PZQ on adult S. mansoni PZQ-resistant and PZQ-susceptible worms survival and fitness.…”

Section: Discussionmentioning

confidence: 99%

Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and -Susceptible Strains Are Different in Presence of Praziquantel

et al. 2016

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Schistosomiasis is one of the most common human parasitic diseases whose socioeconomic impact is only surpassed by malaria. Praziquantel (PZQ) is the only drug commercially available for the treatment of all schistosome species causing disease in humans. However, there has been stronger evidences of PZQ-resistance on Schistosoma mansoni and thus it is very important to study the phenotypic characteristics associated with it. The aim of this study was to evaluate morphological alterations in S. mansoni PZQ-resistant adult worms and eggs, by comparing a PZQ- resistant strain obtained under PZQ drug pressure with a PZQ-susceptible strain. For this, scanning electronic microscopy was used to assess tegumental responsiveness of both strains under PZQ exposure, and optical microscopy allowed the monitoring of worms and eggs in the presence of the drug. Those assays showed that PZQ-susceptible worms exposed to the drug had more severe tegumental damages than the resistant one, which had only minor alterations. Moreover, contrary to what occurred in the susceptible strain, resistant worms were viable after PZQ exposure and gradually regaining full motility after removal of the drug. Eggs from resistant strain parasites are considerably smaller than those from susceptible strain. Our results suggest that there might be a difference in the tegument composition of the resistant strain and that worms are less responsive to PZQ. Changes observed in egg morphology might imply alterations in the biology of schistosomes associated to PZQ-resistance, which could impact on transmission and pathology of the disease. Moreover, we propose a hypothetical scenario where there is a different egg tropism of the S. mansoni resistant strain. This study is the first comparing two strains that only differ in their resistance characteristics, which makes it a relevant step in the search for resistance determinants.

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Antischistosomal activity of aminoalkanethiols, aminoalkanethiosulfuric acids and the corresponding disulfides

Cited by 25 publications

References 38 publications

Potent Schistosomicidal Constituents from Garcinia brasiliensis

Potent Schistosomicidal Constituents from Garcinia brasiliensis

Ultrastructural analysis of miltefosine-induced surface membrane damage in adult Schistosoma mansoni BH strain worms

Morphological Characteristics of Schistosoma mansoni PZQ-Resistant and -Susceptible Strains Are Different in Presence of Praziquantel

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