The anthelmintic meclonazepam activates a schistosome transient receptor potential channel.

Parasitic flatworms cause various clinical and veterinary infections that impart a huge burden worldwide. The most clinically impactful infection is schistosomiasis, a neglected tropical disease caused by parasitic blood flukes. Schistosomiasis is treated with praziquantel (PZQ), an old drug introduced over 40 years ago. New drugs are urgently needed, as while PZQ is broadly effective it suffers from several limitations including poor efficacy against juvenile worms, which may prevent it from being completely curative. An old compound that retains efficacy against juvenile worms is the benzodiazepine meclonazepam (MCLZ). However, host side effects caused by benzodiazepines preclude development of MCLZ as a drug and MCLZ lacks an identified parasite target to catalyze rational drug design for engineering out human host activity. Here, we identify a transient receptor potential ion channel of the melastatin subfamily, named TRPMMCLZ, as a parasite target of MCLZ. MCLZ potently activates Schistosoma mansoni TRPMMCLZ through engagement of a binding pocket within the voltage-sensor-like domain of the ion channel to cause worm paralysis, tissue depolarization, and surface damage. TRPMMCLZ reproduces all known features of MCLZ action on schistosomes, including a lower activity versus Schistosoma japonicum, which is explained by a polymorphism within this voltage-sensor-like domain-binding pocket. TRPMMCLZ is distinct from the TRP channel targeted by PZQ (TRPMPZQ), with both anthelmintic chemotypes targeting unique parasite TRPM paralogs. This advances TRPMMCLZ as a novel druggable target that could circumvent any target-based resistance emerging in response to current mass drug administration campaigns centered on PZQ.

How Does Treatment Coverage and Proportion Never Treated Influence the Success of Schistosoma mansoni Elimination as a Public Health Problem by 2030?

BACKGROUND: The 2030 target for schistosomiasis is elimination as a public health problem (EPHP), achieved when the prevalence of heavy-intensity infection among school-aged children (SAC) reduces to <1%. To achieve this, the new World Health Organization guidelines recommend a broader target of population to include pre-SAC and adults. However, the probability of achieving EPHP should be expected to depend on patterns in repeated uptake of mass drug administration by individuals. METHODS: We employed 2 individual-based stochastic models to evaluate the impact of school-based and community-wide treatment and calculated the number of rounds required to achieve EPHP for Schistosoma mansoni by considering various levels of the population never treated (NT). We also considered 2 age-intensity profiles, corresponding to a low and high burden of infection in adults. RESULTS: The number of rounds needed to achieve this target depends on the baseline prevalence and the coverage used. For low- and moderate-transmission areas, EPHP can be achieved within 7 years if NT ≤10% and NT <5%, respectively. In high-transmission areas, community-wide treatment with NT <1% is required to achieve EPHP. CONCLUSIONS: The higher the intensity of transmission, and the lower the treatment coverage, the lower the acceptable value of NT becomes. Using more efficacious treatment regimens would permit NT values to be marginally higher. A balance between target treatment coverage and NT values may be an adequate treatment strategy depending on the epidemiological setting, but striving to increase coverage and/or minimize NT can shorten program duration.

In vitro and in vivo efficacy of the amiodarone and praziquantel combination against the blood fluke Schistosoma mansoni.

Schistosomiasis, a widespread parasitic disease caused by the blood fluke of the genus Schistosoma, affects over 230 million people, primarily in developing countries. Praziquantel, the sole drug currently approved for schistosomiasis treatment, demonstrates effectiveness against patent infections. A recent study highlighted the antiparasitic properties of amiodarone, an anti-arrhythmic drug, exhibiting higher efficacy than praziquantel against prepatent infections. This study assessed the efficacy of amiodarone and praziquantel, both individually and in combination, against Schistosoma mansoni through comprehensive in vitro and in vivo experiments. In vitro experiments demonstrated synergistic activity (fractional inhibitory concentration index ≤0.5) for combinations of amiodarone with praziquantel. In a murine model of schistosomiasis featuring prepatent infections, treatments involving amiodarone (200 or 400 mg/kg) followed by praziquantel (200 or 400 mg/kg) yielded a substantial reduction in worm burden (60%-70%). Given the low efficacy of praziquantel in prepatent infections, combinations of amiodarone with praziquantel may offer clinical utility in the treatment of schistosomiasis.

Therapeutic efficacy of candidate antischistosomal drugs in a murine model of schistosomiasis mansoni.

Schistosomiasis is a neglected tropical disease associated with considerable morbidity. Praziquantel (PZQ) is effective against adult schistosomes, yet, it has little effect on juvenile stages, and PZQ resistance is emerging. Adopting the drug repurposing strategy as well as assuming enhancing the efficacy and lessening the doses and side effects, the present study aimed to investigate the in vivo therapeutic efficacy of the widely used antiarrhythmic, amiodarone, and diuretic, spironolactone, and combinations of them compared to PZQ. Mice were infected by Schistosoma mansoni "S. mansoni" cercariae (Egyptian strain), then they were divided into two major groups: Early- [3 weeks post-infection (wpi)] and late- [6 wpi] treated. Each group was subdivided into seven subgroups: positive control, PZQ, amiodarone, spironolactone, PZQ combined with amiodarone, PZQ combined with spironolactone, and amiodarone combined with spironolactone-treated groups. Among the early-treated groups, spironolactone had the best therapeutic impact indicated by a 69.4% reduction of total worm burden (TWB), 38.6% and 48.4% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 49%. Whereas, among the late-treated groups, amiodarone combined with PZQ was superior to PZQ alone evidenced by 96.1% reduction of TWB with the total disappearance of female and copula in the liver and intestine, 53.1% and 84.9% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 67.6%. Comparatively, spironolactone was superior to PZQ and amiodarone in the early treatment phase targeting immature stages, while amiodarone had a more potent effect when combined with PZQ in the late treatment phase targeting mature schistosomes.

Biological, biochemical and genotoxicological alterations of Benzylamine on Biomphalaria alexandrina snails and its Schistosoma mansoni larvicidal potential.

Biomphalaria spp. snails are freshwater gastropods that responsible for Schistosoma mansoni transmission. Schistosomiasis is a chronic illness that occurred in underdeveloped regions with poor sanitation. The aim of the present study is to evaluate the molluscicidal activity of benzylamine against B. alexandrina snails and it larvicidal effects on the free larval stages of S. mansoni. Results showed that benzylamine has molluscicidal activity against adult B. alexandrina snails after 24 h of exposure with median lethal concentration (LC50) 85.7 mg/L. The present results indicated the exposure of B. alexandrina snails to LC10 or LC25 of benzylamine resulted in significant decreases in the survival, fecundity (eggs/snail/week) and reproductive rates, acetylcholinesterase, albumin, protein, uric acid and creatinine concentrations, levels of Testosterone (T) and 17ß Estradiol (E), while alkaline phosphatase levels were significantly increased in comparison with control ones. The present results showed that the sub lethal concentration LC50 (85.7 mg/L) of benzylamine has miracidial and cercaricidal activities, where the Lethal Time (LT50) for miracidiae was 17.08 min while for cercariae was 30.6 min. Also, results showed that were decreased significantly after exposure to sub lethal concentrations compared with control. The present results showed that the expression level of NADH dehydrogenase subunit 1 (ND1) genes and cytochrome oxidase subunit I (COI) in B. alexandrina snails exposed to LC10 or LC25 concentrations benzylamine were significantly decreased compared to the control groups. Therefore, benzylamine could be used as effective molluscicide to control schistosomiasis.

In vitro Evaluation of the Antileishmanial and Antischistosomal Activities of p-Coumaric Acid Prenylated Derivatives.

We have evaluated eight p-coumaric acid prenylated derivatives in vitro for their antileishmanial activity against Leishmania amazonensis promastigotes and their antischistosomal activity against Schistosoma mansoni adult worms. Compound 7 ((E)-3,4-diprenyl-4-isoprenyloxycinnamic alcohol) was the most active against L. amazonensis (IC50=45.92 µM) and S. mansoni (IC50=64.25 µM). Data indicated that the number of prenyl groups, the presence of hydroxyl at C9, and a single bond between C7 and C8 are important structural features for the antileishmanial activity of p-coumaric acid prenylated derivatives.

In Silico Comparison of Bioactive Compounds Characterized from Azadirachta indica with an FDA-Approved Drug against Schistosomal Agents: New Insight into Schistosomiasis Treatment.

The burden of human schistosomiasis, a known but neglected tropical disease in Sub-Saharan Africa, has been worrisome in recent years. It is becoming increasingly difficult to tackle schistosomiasis with praziquantel, a drug known to be effective against all Schistosoma species, due to reports of reduced efficacy and resistance. Therefore, this study seeks to investigate the antischistosomal potential of phytochemicals from Azadirachta indica against proteins that have been implicated as druggable targets for the treatment of schistosomiasis using computational techniques. In this study, sixty-three (63) previously isolated and characterized phytochemicals from A. indica were identified from the literature and retrieved from the PubChem database. In silico screening was conducted to assess the inhibitory potential of these phytochemicals against three receptors (Schistosoma mansoni Thioredoxin glutathione reductase, dihydroorotate dehydrogenase, and Arginase) that may serve as therapeutic targets for schistosomiasis treatment. Molecular docking, ADMET prediction, ligand interaction, MMGBSA, and molecular dynamics simulation of the hit compounds were conducted using the Schrodinger molecular drug discovery suite. The results show that Andrographolide possesses a satisfactory pharmacokinetic profile, does not violate the Lipinski rule of five, binds with favourable affinity with the receptors, and interacts with key amino acids at the active site. Importantly, its interaction with dihydroorotate dehydrogenase, an enzyme responsible for the catalysis of the de novo pyrimidine nucleotide biosynthetic pathway rate-limiting step, shows a glide score and MMGBSA of -10.19 and -45.75 Kcal/mol, respectively. In addition, the MD simulation shows its stability at the active site of the receptor. Overall, this study revealed that Andrographolide from Azadirachta indica could serve as a potential lead compound for the development of an anti-schistosomal drug.

Neurological impairment caused by Schistosoma mansoni systemic infection exhibits early features of idiopathic neurodegenerative disease.

Schistosomiasis, a neglected tropical disease caused by trematodes of the Schistosoma genus, affects over 250 million people around the world. This disease has been associated with learning and memory deficits in children, whereas reduced attention levels, impaired work capacity, and cognitive deficits have been observed in adults. Strongly correlated with poverty and lack of basic sanitary conditions, this chronic endemic infection is common in Africa, South America, and parts of Asia and contributes to inhibition of social development and low quality of life in affected areas. Nonetheless, studies on the mechanisms involved in the neurological impairment caused by schistosomiasis are scarce. Here, we used a murine model of infection with Schistosoma mansoni in which parasites do not invade the central nervous system to evaluate the consequences of systemic infection on neurologic function. We observed that systemic infection with S. mansoni led to astrocyte and microglia activation, expression of oxidative stress-induced transcription factor Nrf2, oxidative damage, Tau phosphorylation, and amyloid-ß peptide accumulation in the prefrontal cortex of infected animals. We also found impairment in spatial learning and memory as evaluated by the Morris water maze task. Administration of anthelmintic (praziquantel) and antioxidant (N-acetylcysteine plus deferoxamine) treatments was effective in inhibiting most of these phenotypes, and the combination of both treatments had a synergistic effect to prevent such changes. These data demonstrate new perspectives toward the understanding of the pathology and possible therapeutic approaches to counteract long-term effects of systemic schistosomiasis on brain function.

Systematically improved in vitro culture conditions reveal new insights into the reproductive biology of the human parasite Schistosoma mansoni.

Schistosomes infect over 200 million people. The prodigious egg output of these parasites is the sole driver of pathology due to infection, yet our understanding of sexual reproduction by schistosomes is limited because normal egg production is not sustained for more than a few days in vitro. Here, we describe culture conditions that support schistosome sexual development and sustained egg production in vitro. Female schistosomes rely on continuous pairing with male worms to fuel the maturation of their reproductive organs. Exploiting these new culture conditions, we explore the process of male-stimulated female maturation and demonstrate that physical contact with a male worm, and not insemination, is sufficient to induce female development and the production of viable parthenogenetic haploid embryos. We further report the characterization of a nuclear receptor (NR), which we call Vitellogenic Factor 1 (VF1), that is essential for female sexual development following pairing with a male worm. Taken together, these results provide a platform to study the fascinating sexual biology of these parasites on a molecular level, illuminating new strategies to control schistosome egg production.

A rotifer-derived paralytic compound prevents transmission of schistosomiasis to a mammalian host.

Schistosomes are parasitic flatworms that infect over 200 million people, causing the neglected tropical disease, schistosomiasis. A single drug, praziquantel, is used to treat schistosome infection. Limitations in mass drug administration programs and the emergence of schistosomiasis in nontropical areas indicate the need for new strategies to prevent infection. It has been known for several decades that rotifers colonizing the schistosome's snail intermediate host produce a water-soluble factor that paralyzes cercariae, the life cycle stage infecting humans. In spite of its potential for preventing infection, the nature of this factor has remained obscure. Here, we report the purification and chemical characterization of Schistosome Paralysis Factor (SPF), a novel tetracyclic alkaloid produced by the rotifer Rotaria rotatoria. We show that this compound paralyzes schistosome cercariae and prevents infection and does so more effectively than analogous compounds. This molecule provides new directions for understanding cercariae motility and new strategies for preventing schistosome infection.

Antischistosomal tetrahydro-γ-carboline sulfonamides.

We discovered tetrahydro-γ-carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro-γ-carboline substructures were required for high antischistosomal activity. Increasing polarity improved solubility and metabolic stability but decreased antischistosomal activity. We identified two compounds with IC50 values <5 µM against ex vivo Schistosoma mansoni.

Algal-Derived Halogenated Sesquiterpenes from Laurencia dendroidea as Lead Compounds in Schistosomiasis Environmental Control.

Schistosomiasis has been controlled for more than 40 years with a single drug, praziquantel, and only one molluscicide, niclosamide, raising concern of the possibility of the emergence of resistant strains. However, the molecular targets for both agents are thus far unknown. Consequently, the search for lead compounds from natural sources has been encouraged due to their diverse structure and function. Our search for natural compounds with potential use in schistosomiasis control led to the identification of an algal species, Laurencia dendroidea, whose extracts demonstrated significant activity toward both Schistosoma mansoni parasites and their intermediate host snails Biomphalaria glabrata. In the present study, three seaweed-derived halogenated sesquiterpenes, (-)-elatol, rogiolol, and obtusol are proposed as potential lead compounds for the development of anthelminthic drugs for the treatment of and pesticides for the environmental control of schistosomiasis. The three compounds were screened for their antischistosomal and molluscicidal activities. The screening revealed that rogiolol exhibits significant activity toward the survival of adult worms, and that all three compounds showed activity against S. mansoni cercariae and B. glabrata embryos. Biomonitored fractioning of L. dendroidea extracts indicated elatol as the most active compound toward cercariae larvae and snail embryos.

Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment.

Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29-14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate OXA deployment. We conclude that standing variation for OXA resistance is widespread in S. mansoni.

Intestinal schistosomiasis among preschool and school-aged children in a rural setting near Alexandria: initiative for elimination.

OBJECTIVE: To assess the status of intestinal schistosomiasis among preschool-aged (PSAC) and school-aged children (SAC) and to compare the efficacy of praziquantel (PZQ) in both groups. METHODS: The study was conducted on 400 children; 103 PSAC and 297 SAC. Diagnosis of Schistosoma mansoni was based on triplicate Kato-Katz thick smears from a single stool sample. To identify the missed cases by Kato-Katz, 120 randomly selected negative cases (38 PSAC and 82 SAC) were screened by real-time PCR. All S. mansoni-positive cases by Kato-Katz were treated by crushed PZQ tablets. Four weeks after treatment, the cure rate was assessed by Kato-Katz smears and real-time PCR. RESULTS: The prevalence of S. mansoni with Kato-Katz was 7.8% among PSAC and 7.4% among SAC. Most of children (63.3%) had light-intensity infection. The cure rate was 100% among PSAC by both techniques, and 91%, and 77.2% among SAC by Kato-Katz and real-time PCR, respectively. In the 120 stool samples screened by real-time PCR, S. mansoni prevalence was 25%; 15.8% and 29.3% were among PSAC and SAC respectively. Treated cases showed a lower range of Ct values than untreated cases. Two melting temperature ranges (Tm = 83-87°C and 89-93°C) were recognised among uncured cases which may point to S. mansoni genetic variability. CONCLUSION: Continuous monitoring and inclusion of PSAC in schistosomiasis control programmes are crucial. Real-time PCR and other molecular tools are recommended for evaluation of the true prevalence, assessment of cure and further studies on genetic diversity.

High-resolution AP-SMALDI MSI as a tool for drug imaging in Schistosoma mansoni.

Schistosoma mansoni is a parasitic flatworm causing schistosomiasis, an infectious disease affecting several hundred million people worldwide. Schistosomes live dioeciously, and upon pairing with the male, the female starts massive egg production, which causes pathology. Praziquantel (PZQ) is the only drug used, but it has an inherent risk of resistance development. Therefore, alternatives are needed. In the context of drug repurposing, the cancer drug imatinib was tested, showing high efficacy against S. mansoni in vitro. Besides the gonads, imatinib mainly affected the integrity of the intestine in males and females. In this study, we investigated the potential uptake and distribution of imatinib in adult schistosomes including its distribution kinetics. To this end, we applied for the first time atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) for drug imaging in paired S. mansoni. Our results indicate that imatinib was present in the esophagus and intestine of the male as early as 20 min after in vitro exposure, suggesting an oral uptake route. After one hour, the drug was also found inside the paired female. The detection of the main metabolite, N-desmethyl imatinib, indicated metabolization of the drug. Additionally, a marker signal for the female ovary was successfully applied to facilitate further conclusions regarding organ tropism of imatinib. Our results demonstrate that AP-SMALDI MSI is a useful method to study the uptake, tissue distribution, and metabolization of imatinib in S. mansoni. The results suggest using AP-SMALDI MSI also for investigating other antiparasitic compounds and their metabolites in schistosomes and other parasites.

The Prospective Use of Brazilian Marine Macroalgae in Schistosomiasis Control.

Schistosomiasis is a parasitic disease that affects more than 250 million people. The treatment is limited to praziquantel and the control of the intermediate host with the highly toxic molluscicidal niclosamide. Marine algae are a poorly explored and promising alternative that can provide lead compounds, and the use of multivariate analysis could contribute to quicker discovery. As part of our search for new natural compounds with which to control schistosomiasis, we screened 45 crude extracts obtained from 37 Brazilian seaweed species for their molluscicidal activity against Biomphalaria glabrata embryos and schistosomicidal activities against Schistosoma mansoni. Two sets of extracts were taxonomically grouped for metabolomic analysis. The extracts were analyzed by GC-MS, and the data were subjected to Pattern Hunter and Pearson correlation tests. Overall, 22 species (60%) showed activity in at least one of the two models. Multivariate analysis pointed towards 3 hits against B. glabrata veliger embryos in the Laurencia/Laurenciella set, 5 hits against B. glabrata blastula embryos, and 31 against S. mansoni in the Ochrophyta set. Preliminary annotations suggested some compounds such as triquinane alcohols, prenylated guaianes, dichotomanes, and xenianes. Despite the putative identification, this work presents potential candidates and can guide future isolation and identification.

Effect of methyl gallate on immune response of Biomphalaria alexandrina (Ehrenberg, 1831) snails to infection with Schistosoma mansoni (Sambon, 1907).

Schistosomiasis still affects a lot of people in many developing countries. Reducing the disease dissemination has been the target of various studies. As methyl gallate has antioxidant properties, it is assumed that it can be a good candidate for stimulating the immune response of snails. So, the aim of this work is to investigate the potential of using methyl gallate as an immunostimulant to Biomphalaria alexandrina snails in order to prevent the development of invading miracidia into infective cercariae. The infected snails were exposed to three concentrations of methyl gallate for two periods: 24 and 72 h. The results indicated that the most effective concentration was the lowest one: 125 mg/L of methyl gallate for 72 h, as it reduced both infection rate and mean number of shed cercariae. Also, it increased the total number of snails' hemocytes in hemolymph, which were observed in head-foot region and digestive gland of treated snails surrounding degenerated sporocysts and cercariae. In addition, hydrogen peroxide showed its highest content in tissues of snails exposed to 125 mg/L of methyl gallate for 72 h. In conclusion, methyl gallate can be considered as one of the most promising immunostimulants of B. alexandrina snails against infection with Schistosoma mansoni.

In vitro and in vivo evaluation of cnicin from blessed thistle (Centaurea benedicta) and its inclusion complexes with cyclodextrins against Schistosoma mansoni.

Schistosomiasis, caused by a blood fluke of the genus Schistosoma, afflicts over 230 million people worldwide. Treatment of the disease relies on just one drug, praziquantel. Cnicin (Cn) is the sesquiterpene lactone found in blessed thistle (Centaurea benedicta) that showed antiparasitic activities but has not been evaluated against Schistosoma. However, cnicin has poor water solubility, which may limit its antiparasitic activities. To overcome these restrictions, inclusion complexes with cyclodextrins may be used. In this work, we evaluated the in vitro and in vivo antischistosomal activities of cnicin and its complexes with ß-cyclodextrin (ßCD) and 2-hydroxypropyl-ß-cyclodextrin (HPßCD) against Schistosoma mansoni. Cnicin were isolated from C. benedicta by chromatographic fractionation. Complexes formed by cnicin and ßCD (Cn/ßCD), as well as by cnicin and HPßCD (Cn/HPßCD), were prepared by coprecipitation and characterized. In vitro schistosomicidal assays were used to evaluate the effects of cnicin and its complexes on adult schistosomes, while the in vivo antischistosomal assays were evaluated by oral and intraperitoneal routes. Results showed that cnicin caused mortality and tegumental alterations in adult schistosomes in vitro, also showing in vivo efficacy after intraperitoneal administration. The oral treatment with cnicin or Cn/ßCD showed no significant worm reductions in a mouse model of schistosomiasis. In contrast, Cn/HPßCD complex, when orally or intraperitoneally administered to S. mansoni-infected mice, decreased the total worm load, and markedly reduced the number of eggs, showing high in vivo antischistosomal effectiveness. Permeability studies, using Nile red, indicated that HPßCD complex may reach the tegument of adult schistosomes in vivo. These results demonstrated the antischistosomal potential of cnicin in preparations with HPßCD.

Synthetic Aurones: New Features for Schistosoma mansoni Therapy.

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.

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

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.