Worm Killing Research Articles

To Target or Not to Target Schistosoma mansoni Cyclic Nucleotide Phosphodiesterase 4A?

Schistosomiasis is a neglected tropical disease with high morbidity. Recently, the Schistosoma mansoni phosphodiesterase SmPDE4A was suggested as a putative new drug target. To support SmPDE4A targeted drug discovery, we cloned, isolated, and biochemically characterized the full-length and catalytic domains of SmPDE4A. The enzymatically active catalytic domain was crystallized in the apo-form (PDB code: 6FG5) and in the cAMP- and AMP-bound states (PDB code: 6EZU). The SmPDE4A catalytic domain resembles human PDE4 more than parasite PDEs because it lacks the parasite PDE-specific P-pocket. Purified SmPDE4A proteins (full-length and catalytic domain) were used to profile an in-house library of PDE inhibitors (PDE4NPD toolbox). This screening identified tetrahydrophthalazinones and benzamides as potential hits. The PDE inhibitor NPD-0001 was the most active tetrahydrophthalazinone, whereas the approved human PDE4 inhibitors roflumilast and piclamilast were the most potent benzamides. As a follow-up, 83 benzamide analogs were prepared, but the inhibitory potency of the initial hits was not improved. Finally, NPD-0001 and roflumilast were evaluated in an in vitro anti-S. mansoni assay. Unfortunately, both SmPDE4A inhibitors were not effective in worm killing and only weakly affected the egg-laying at high micromolar concentrations. Consequently, the results with these SmPDE4A inhibitors strongly suggest that SmPDE4A is not a suitable target for anti-schistosomiasis therapy.

Immunological Considerations for Schistosoma Vaccine Development: Transitioning to Endemic Settings.

Despite mass drug administration programmes with praziquantel, the prevalence of schistosomiasis remains high. A vaccine is urgently needed to control transmission of this debilitating disease. As some promising schistosomiasis vaccine candidates are moving through pre-clinical and clinical testing, we review the immunological challenges that these vaccine candidates may encounter in transitioning through the clinical trial phases in endemic settings. Prior exposure of the target population to schistosomes and other infections may impact vaccine response and efficacy and therefore requires considerable attention. Schistosomes are known for their potential to induce T-reg/IL-10 mediated immune suppression in populations which are chronically infected. Moreover, endemicity of schistosomiasis is focal whereby target and trial populations may exhibit several degrees of prior exposure as well as in utero exposure which may increase heterogeneity of vaccine responses. The age dependent distribution of exposure and development of acquired immunity, and general differences in the baseline immunological profile, adds to the complexity of selecting suitable trial populations. Similarly, prior or concurrent infections with other parasitic helminths, viral and bacterial infections, may alter immunological responses. Consequently, treatment of co-infections may benefit the immunogenicity of vaccines and may be considered despite logistical challenges. On the other hand, viral infections leave a life-long immunological imprint on the human host. Screening for serostatus may be needed to facilitate interpretation of vaccine responses. Co-delivery of schistosome vaccines with PZQ is attractive from a perspective of implementation but may complicate the immunogenicity of schistosomiasis vaccines. Several studies have reported PZQ treatment to induce both transient and long-term immuno-modulatory effects as a result of tegument destruction, worm killing and subsequent exposure of worm antigens to the host immune system. These in turn may augment or antagonize vaccine immunogenicity. Understanding the complex immunological interactions between vaccine, co-infections or prior exposure is essential in early stages of clinical development to facilitate phase 3 clinical trial design and implementation policies. Besides well-designed studies in different target populations using schistosome candidate vaccines or other vaccines as models, controlled human infections could also help identify markers of immune protection in populations with different disease and immunological backgrounds.

The promising antischistosomal activity of oleic acid-loaded polymeric nanocapsules for oral administration

Neglected Tropical Diseases, such as schistosomiasis, still affect thousands of people, presenting high morbidity rates. Currently, praziquantel is the only drug available for the treatment, disclosing the urgency of developing new treatment alternatives. Oleic acid is commonly used as a permeation promoter, inducing the disruption of the membrane's lipid structure. It is an exciting characteristic for the oleic acid to act on the Schistosoma mansoni worm tegument as a therapeutic target. However, it possesses low aqueous solubility and oral bioavailability. Thus, the oleic acid encapsulation in a nanostructured system, such as polymeric nanocapsules, can improve its properties and efficacy. This study aimed to develop, characterize, and evaluate the in vitro cytotoxicity and antischistosomal effect of oleic acid-loaded nanocapsules. We employed the interfacial deposition method for the oleic acid-loaded polymeric nanocapsules preparation. We performed physicochemical characterization, in vitro cytotoxicity, and antischistosomal effect studies for the designed nanocapsules. The oleic acid-loaded nanocapsules are spherical, with a smooth surface, average size around 200 nm, low polydispersity index (<0.3), and zeta potential higher than (−) 30 mV. All oleic acid was encapsulated in the nanocapsules. The cell viability was greater than 70% for all treatments with oleic acid-loaded nanocapsules, except for samples diluted 1:10 (v/v), and greater than 100% for some dilutions. Sub-lethal concentrations (12.5 and 25 μg/mL) of nanocapsules reduce egg production and worms' motor activity. The oleic acid-loaded polymeric nanocapsules cause death in a concentration-dependent manner, showing 100% of worms mortality from 200 μg/mL in 4 h of incubation and 50 μg/mL in 24 h. Besides, optical microscopy revealed that oleic acid-loaded polymeric nanocapsules caused moderate to intense damage of the tegument dorsal surface, which is essential to cause the worm killing. Finally, the developed oleic acid-loaded polymeric nanocapsules show considerable in vitro activity against S. mansoni, promising a new treatment option.

Identification of plumbagin as an effective chemotherapeutic agent for treatment of Gyrodactylus infections

Monogenean parasites are responsible for severe economic losses of both freshwater and marine aquaculture industries. Current chemotherapeutic treatments are consuming, expensive, and harmful to water quality and human health. Medicinal plants are a reliable source of alternative anthelmintic agents. In the pursuit of novel anti-monogenean drugs, in vivo anthelminthic efficacy of 26 selected phytochemical compounds was studied, by choosing Gyrodactylus kobayashi infecting goldfish (Carassius auratus) as a model. The screening results showed that four compounds (plumbagin (PLB), thymoquinone, osthole and psoralen) had the highest activity against G. kobayashii with EC99 value ranging from 0.4 to 4.0 mg/L after 48-h exposure. Among these active compounds, PLB was the most efficacious one and selected for the next study. In vitro trials revealed the clear anti-parasitic effects of PLB, with complete death at 45 min of exposure at a concentration of 2.0 mg/L, withdrawal of PLB afterward did not lead to the recovery of the exposed parasites. Bathing G. kobayashii infected goldfish in PLB also significantly reduced the worm burden, with an extremely low EC50 value of 0.09 mg/L after 48-h immersion. The results also showed that one short bath using very low concentrations of 0.4–0.7 mg/L for 30–60 min was effective in eliminating G. kobayashii infection with no visible fish toxicity. Acute toxicity assay indicated the 48-h LC50 of PLB against goldfish was 0.657 mg/L. Furthermore, SEM analysis displayed that PLB-mediated worm killing was associated with the tegumental damages. As seen by TEM, in vivo treatment against G. kobayashii with PLB also caused vacuolization and lysis of parasite's tegument, besides, differing degrees of damage to vitelline cells were observed in treated worms. Collectively, simple chemical structure along with the potent efficacy demonstrated that PLB could serve as an ideal leading compound in the development of a commercial drug to control Gyrodactylus infections in aquaculture

Manniindole, an indole derivative from the roots of Anonidium mannii and combined antischistosomal and enzymatic activities

A new alkaloid, manniindole 1, together with four known compounds: aristolactam AII 2, aristolactam BII 3, piperolactam D 4 and polycarpol 5 were isolated from the crude extract EtOH-H2O (8:2) of the roots of Anonidium mannii by chromatographic separation. The structure elucidation was performed on the basis of a spectroscopic analysis (IR, HRESI MS, 1D and 2D NMR) as well as a comparison of their spectral data with those reported in the literature. For the first time, the crude extract and those isolated compounds were evaluated for their anti-schistosomal activity against Schistosoma mansoni and for cytotoxicity activity against Huh7 and A549 cells. Furthermore, they were also tested in vitro on the recent characterized Schistosoma mansoni NAD+ catabolizing enzyme (SmNACE) for their impact on this enzyme which is localized on the outer surface of the adult parasite. Compound 2 displayed quite good worm killing capability, while 4 showed significant inhibition of SmNACE.

An iterative process produces oxamniquine derivatives that kill the major species of schistosomes infecting humans.

Currently there is only one method of treatment for human schistosomiasis, the drug praziquantel. Strong selective pressure has caused a serious concern for a rise in resistance to praziquantel leading to the necessity for additional pharmaceuticals, with a distinctly different mechanism of action, to be used in combination therapy with praziquantel. Previous treatment of Schistosoma mansoni included the use of oxamniquine (OXA), a prodrug that is enzymatically activated in S. mansoni but is ineffective against S. haematobium and S. japonicum. The oxamniquine activating enzyme was identified as a S. mansoni sulfotransferase (SmSULT-OR). Structural data have allowed for directed drug development in reengineering oxamniquine to be effective against S. haematobium and S. japonicum. Guided by data from X-ray crystallographic studies and Schistosoma worm killing assays on oxamniquine, our structure-based drug design approach produced a robust SAR program that tested over 300 derivatives and identified several new lead compounds with effective worm killing in vitro. Previous studies resulted in the discovery of compound CIDD-0066790, which demonstrated broad-species activity in killing of schistosome species. As these compounds are racemic mixtures, we tested and demonstrate that the R enantiomer CIDD-007229 kills S. mansoni, S. haematobium and S. japonicum better than the parent drug (CIDD-0066790). The search for derivatives that kill better than CIDD-0066790 has resulted in a derivative (CIDD- 149830) that kills 100% of S. mansoni, S. haematobium and S. japonicum adult worms within 7 days. We hypothesize that the difference in activation and thus killing by the derivatives is due to the ability of the derivative to fit in the binding pocket of each sulfotransferase (SmSULT-OR, ShSULT-OR, SjSULT-OR) and to be efficiently sulfated. The purpose of this research is to develop a second drug to be used in conjunction with praziquantel to treat the major human species of Schistosoma. Collectively, our findings show that CIDD-00149830 and CIDD-0072229 are promising novel drugs for the treatment of human schistosomiasis and strongly support further development and in vivo testing.

Efficacy and antiparasitic mechanism of curdione from Curcuma zedoaria against Gyrodactylus kobayashii in goldfish

Monogeneans are principally ectoparasites of fish with a global distribution and result in fish morbidity and mortality in aquaculture. Since current treatments mainly rely on the application of toxic or unapproved chemicals, there is an urgent need to identify new anthelmintic agents. In the present study, in vivo anthelminthic activities of 33 selected medicinal plants were investigated against Gyrodactylus kobayashii, a monogenean parasite infecting goldfish (Carassius auratus). The screening results showed that the methanol extracts of Curcuma zedoaria and Peucedanum praeruptorum had the highest activity against G. kobayashii. The concentration required to kill all parasites of two extracts was both 30 mg/L within 48 h of exposure, while C. zedoaria methanol extract showed lower toxicity to goldfish and was selected for the next study. Subsequently, two major sesquiterpene compounds from C. zedoaria, curdione and curcumenol were further tested for anthelminthic efficacy. The results revealed that only curdione demonstrated in vitro and in vivo antiparasitic effects, 12 mg/L killed 87.04% of G. kobayashii after 2 h in in vitro trials. And bathing G. kobayashii-infected goldfish in curdione induced significant reduction in a total worm burden, with EC50 values of 1.323 and 0.885 mg/L after 24 and 48-h immersion, respectively, and 100% efficacy was achieved at a concentration of 4.0 mg/L after 48 h. Furthermore, to gain insight into the plausible mechanism of anthelminthic activity of curdione, its effects on the ultrastructural alterations of G. kobayashii were performed in vivo by SEM which displayed obvious tegumental damages. Further confirmation of the significant declines of ATP contents in worms were obtained after both in vitro and in vivo treatments with curdione. These findings indicated that curdione mediated worm killing was associated with tegumental damages and energy insufficient. The results suggested that curdione has the potential as an alternative natural compound for the control of Gyrodactylus infections.

Ectopic suicide inhibition of thioredoxin glutathione reductase

Selective suicide inhibitors represent a seductively attractive approach for inactivation of therapeutically relevant enzymes since they are generally devoid of off-target toxicity in vivo. While most suicide inhibitors are converted to reactive species at enzyme active sites, theoretically bioactivation can also occur in ectopic (secondary) sites that have no known function. Here, we report an example of such an “ectopic suicide inhibition”, an unprecedented bioactivation mechanism of a suicide inhibitor carried out by a non-catalytic site of thioredoxin glutathione reductase (TGR). TGR is a promising drug target to treat schistosomiasis, a devastating human parasitic disease. Utilizing hits selected from a high throughput screening campaign, time-resolved X-ray crystallography, molecular dynamics, mass spectrometry, molecular modeling, protein mutagenesis and functional studies, we find that 2-naphtholmethylamino derivatives bound to this novel ectopic site of Schistosoma mansoni (Sm)TGR are transformed to covalent modifiers and react with its mobile selenocysteine-containing C-terminal arm. In particular, one 2-naphtholmethylamino compound is able to specifically induce the pro-oxidant activity in the inhibited enzyme. Since some 2-naphtholmethylamino analogues show worm killing activity and the ectopic site is not conserved in human orthologues, a general approach to development of novel and selective anti-parasitic therapeutics against schistosoma is proposed.

Inflammasome-Independent Role for NLRP3 in Controlling Innate Antihelminth Immunity and Tissue Repair in the Lung.

Alternatively activated macrophages are essential effector cells during type 2 immunity and tissue repair following helminth infections. We previously showed that Ym1, an alternative activation marker, can drive innate IL-1R-dependent neutrophil recruitment during infection with the lung-migrating nematode, Nippostrongylus brasiliensis, suggesting a potential role for the inflammasome in the IL-1-mediated innate response to infection. Although inflammasome proteins such as NLRP3 have important proinflammatory functions in macrophages, their role during type 2 responses and repair are less defined. We therefore infected Nlrp3 -/- mice with N. brasiliensis Unexpectedly, compared with wild-type (WT) mice, infected Nlrp3 -/- mice had increased neutrophilia and eosinophilia, correlating with enhanced worm killing but at the expense of increased tissue damage and delayed lung repair. Transcriptional profiling showed that infected Nlrp3 -/- mice exhibited elevated type 2 gene expression compared with WT mice. Notably, inflammasome activation was not evident early postinfection with N. brasiliensis, and in contrast to Nlrp3 -/- mice, antihelminth responses were unaffected in caspase-1/11-deficient or WT mice treated with the NLRP3-specific inhibitor MCC950. Together these data suggest that NLRP3 has a role in constraining lung neutrophilia, helminth killing, and type 2 immune responses in an inflammasome-independent manner.

Screening of a PDE-focused library identifies imidazoles with in vitro and in vivo antischistosomal activity

We report the evaluation of 265 compounds from a PDE-focused library for their antischistosomal activity, assessed in vitro using Schistosoma mansoni. Of the tested compounds, 171 (64%) displayed selective in vitro activity, with 16 causing worm hypermotility/spastic contractions and 41 inducing various degrees of worm killing at 100 μM, with the surviving worms displaying sluggish movement, worm unpairing and complete absence of eggs. The compounds that did not affect worm viability (n = 72) induced a complete cessation of ovipositing. 82% of the compounds had an impact on male worms whereas female worms were barely affected. In vivo evaluation in S. mansoni-infected mice with the in vitro ‘hit’ NPD-0274 at 20 mg/kg/day orally for 5 days resulted in worm burden reductions of 29% and intestinal tissue egg load reduction of 35% at 10 days post-treatment. Combination of praziquantel (PZQ) at 10 mg/kg/day for 5 days with NPD-0274 or NPD-0298 resulted in significantly higher worm killing than PZQ alone, as well as a reduction in intestinal tissue egg load, disappearance of immature eggs and an increase in the number of dead eggs.

Design, Synthesis, and Characterization of Novel Small Molecules as Broad Range Antischistosomal Agents.

Schistosomiasis is a major human parasitic disease afflicting more than 250 million people, historically treated with chemotherapies praziquantel or oxamniquine. Since oxamniquine is species-specific, killing Schistosoma mansoni but not other schistosome species (S. haematobium or S. japonicum) and evidence for drug resistant strains is growing, research efforts have focused on identifying novel approaches. Guided by data from X-ray crystallographic studies and Schistosoma worm killing assays on oxamniquine, our structure-based drug design approach produced a robust structure-activity relationship (SAR) program that identified several new lead compounds with effective worm killing. These studies culminated in the discovery of compound 12a, which demonstrated broad-species activity in killing S. mansoni (75%), S. haematobium (40%), and S. japonicum (83%).

Arctigenin: An emerging candidate against infections of Gyrodactylus

Gyrodactylosis is a common parasitic disease that affects both farmed and wild fish. Current strategies of chemotherapy are not always satisfactory, requiring the discovery of new anthelmintic agents. Arctigenin is a natural dibenzylbutyrolactone lignin present in several plants with many biological activities. In this study, in vitro and in vivo anthelminthic efficacy of arctigenin against Gyrodactylus kobayashii in goldfish (Carassius auratus) is reported for the first time. In in vitro trials, exposure to arctigenin caused rapid declines in motility and ultimate death of worms. A positive correlation was seen between arctigenin concentrations and the time to parasite death, which, at the highest concentration of 8 mg/L occurred at 33 min. Bathing G. kobayashii-infected goldfish in arctigenin significantly reduced infection prevalences and intensities as compared to the control, with EC50 values of 1.85 and 1.58 mg/L after 24 and 48-h exposure, respectively, with 100% efficacy against G. kobayashii at 4.0 mg/L after only 4 h. Acute toxicity assay indicated that the LC50 of arctigenin against goldfish after 96-h exposure was 11.63 mg/L, which was 6.29 times higher than the 24 h EC50. The expression of four xenobiotic sensitive genes (cyp1a, hsp70, gst and sod) were significantly altered in the initial 48 h after arctigenin treatment, but had a tendency of returning to the initial level of gene expression after 96 h. In addition, SEM and TEM were used to study the specific action of arctigenin against gyrodactylids. SEM revealed that arctigenin-mediated worm killing was associated with tegumental damage and with damage seen by TEM to the mitochondria may be a cause of parasite death. Collectively, these findings demonstrate the potential of arctigenin as an alternative natural compound for controlling infections of Gyrodactylus. With further medicinal chemistry optimization, more potent arctigenin analogues offer promise for future combinatorial or replacement anthelmintic control

In vivo screening platform for shiga toxin-producing Escherichia coli (STEC) using Caenorhabditis elegans as a model.

Shiga toxin-producing Escherichia coli (STEC) strains are the main cause of bacillary dysentery, although STEC strains generally induce milder disease symptoms compared to Shigella species. This study aimed to determine the virulence of STEC using the nematode Caenorhabditis elegans as a model host. Worm killing, fertility and bacterial colonisation assays were performed to examine the potential difference in the virulence of STEC strains compared to that of the control E. coli OP50 strains on which worms were fed. A statistically significant difference in the survival rates of C. elegans was observed in that the STEC strains caused death in 8–10 days and the E. coli OP50 strains caused death in 15 days. STEC strains severely reduced the fertility of the worms. The intestinal load of bacteria in the adult stage nematodes harbouring the E. coli OP50 strains was found to be 3.5 log CFU mL-1. In contrast, the STEC strains E15, E18 and E22 harboured 4.1, 4.2 and 4.7 log CFU ml−1 per nematode, respectively. The heat-killed STEC strains significantly increased the longevity of the worms compared to the non-heated STEC strains. In addition, PCR-based genomic profiling of shiga toxin genes, viz., stx1 and stx2, identified in selected STEC strains revealed that these toxins may be associated with the virulence of the STEC strains. This study demonstrated that C. elegans is an effective model to examine and compare the pathogenicity and virulence variation of STEC strains to that of E. coli OP50 strains.

Antiparasitic activity of nerolidol in a mouse model of schistosomiasis

Schistosomiasis is a major public health problem worldwide, especially in poor communities. Since praziquantel is currently the only drug available to treat schistosomiasis, there is an urgent need to identify new antischistosomal drugs. Nerolidol is a sesquiterpene present as an essential oil in several plants that has been approved by the FDA. This study evaluated the in vivo antischistosomal activity of nerolidol in a mouse model of schistosomiasis infected with either adult or juvenile stages of Schistosoma mansoni. A single dose of nerolidol (100, 200 or 400 mg/kg) administered orally to mice infected with adult schistosomes resulted in a reduction in worm burden and egg production. Treatment with the highest nerolidol dose (400 mg/kg) caused significant reduction in a total worm burden of 70.06% (P < 0.001). Additionally, the technique of quantitative and qualitative oograms showed that a single 400 mg/kg nerolidol dose achieved an immature egg reduction of 84.6% (P < 0.001). In faecal samples, the Kato–Katz method also revealed a reduction of 75.2% in eggs/g at a dose of 400 mg/kg (P < 0.001). Furthermore, scanning electron microscopy revealed that nerolidol-mediated worm killing was associated with tegumental damage. In contrast to activity against adult S. mansoni infection, oral treatment with nerolidol 400 mg/kg had low efficacy in mice harbouring juvenile schistosomes. Since nerolidol is already in use globally as a food additive and has a proven safety record, evaluation of this natural compound's potential for treatment of schistosomiasis could be entirely cost effective in the near future.

Examining the function of chemokine receptor deficient-monocytes during infection with Nippostrongylus brasiliensis

Abstract Nippostrongylus brasiliensis (Nb) is a murine helminth that acutely infects the lungs and the small intestine, and induces a strong Th2 immune response, which includes contributions from innate immune cells such as monocytes. CCR2, the receptor for MCP1, which is expressed primarily on monocytes, was predictably important for monocyte recruitment during Nb infection. However, it was also shown to be necessary to control hemorrhaging as CCR2−/− mice had more blood in the bronchoalveolar lavage fluid compared to wild-type (WT) mice. In addition, CCR2−/− mice produced higher egg burden and more viable worms based on parasite ATP assays. Signaling through CX3CR1, another receptor expressed on monocytes provoked the opposite phenotype. CX3CR1 was not crucial for cellular recruitment after infection, but Nb from CX3CR1−/− mice produced less eggs and were less viable than Nb from WT mice. To investigate potential mechanisms by which monocytes influence worm viability, infective stage Nb (L3) were co-cultured with sorted Ly6c+ monocytes from CX3CR1 WT or knockout (ko) mice. After 5 days in culture, Nb incubated with ko Ly6c+ cells were less motile than Nb cultured with WT Ly6c+ cells. Taken together, these data indicate that CCR2-dependent infiltrating monocytes control inflammation and promote worm killing, while CX3CR1 signaling in monocytes promotes worm viability potentially by influencing worm motility.

Antischistosomal activity of N,N'-arylurea analogs against Schistosoma japonicum.

Although the antischistosomal activities of N,N'-arylurea analogs were reported, systematic structure-activity relationships have not been conducted. In this Letter, we reported the design, synthesis and evaluation of 45 N,N'-arylurea analogs. Among these prepared compounds, 13 compounds were urea linker modified and 32 were N,N'-arylurea derivatives. The activity evaluation revealed 12 analogs exhibited IC50 values lower than 22.6μM, and 7 of them had IC50 less than 10μM against the juvenile Schistosoma japonicum in vitro. Their worm killing potency was even higher against adult worm. Unfortunately, low to moderate worm burden reduction of 0-33.4% was recorded after administration of a single oral dose of 200mg/kg or 400mg/kg to mice harboring S. japonicum.

Enhancing insecticide activity of anacardic acid by intercalating it into MgAl layered double hydroxides nanoparticles

MgAl layered double hydroxides nanoparticles (LDHs) are known as the useful materials in agrochemsitry. LDHs can be used as a bio-insecticide carrier to enhance insecticide’s activity efficiency. In our study, to improve the insecticide activity of anacardic acid, an extract from cashew nut shell liquid, we intercalated it MgAl layered double hydroxides nanoparticles. Different hybridization between anacardic acid and LDHs (37, 74, 148, and 296µg/mL) (L-As) were made and tested on the survivals of cutworms (Spodoptera litura). L-As or free anacardic acid was sprayed directly on the leaves mustard to feed cutworms or directly on the skin of cutworms. Our results showed that in all L-As treatments, the worm killing efficiency was higher than the free anacardic acid treatment.&#x0D; Hạt nano lớp đôi hydroxides MgAl (LDHs) được biết đến như là những vật liệu hữu ích trong nông ngành hóa học nông nghiệp. LDHs có thể được dùng như là một loại chất mang cho thuốc trừ sâu sinh học để tăng cường hiệu lực diệt sâu. Trong nghiên cứu này, để tăng cường hiệu lực diệt sâu của anacardic acid, một loại hoạt chất được chiết từ dầu vỏ hạt điều, chúng tôi đã gắn chèn nó lên hạt nano lớp đôi hydroxides MgAl. Các nồng độ khác nhau của dạng lai của anacardic và LDHs (37, 74, 148 và 296µg/mL) (L-As) đã được kiểm tra tỷ lệ sống của ấu trùng sâu khoang (Spodoptera litura). Các nghiệm thức L-As và dạng anacardic acid tự do đã được phun lên lá rau cải ngọt cho ấu trùng sâu ăn hoặc phun trực tiếp lên da ấu trùng sâu. Kết quả cho thấy, tất cả các công thức có xử lý bằng L-As, hiệu lực diệt ấu trùng sâu đều cao hơn so với dạng anacardic acid ở trạng thái tự do.

Synthesis and SAR Studies of Praziquantel Derivatives with Activity against Schistosoma japonicum

The synthesis and structure-activity relationship (SAR) studies of praziquantel derivatives with activity against adult Schistosoma japonicum are described. Several of them showed better worm killing activity than praziquantel and could serve as leads for further optimization.

Development of a novel class of pyrrolo-[1,2,5]benzothiadiazepine derivatives as potential anti-schistosomal agents

Analogues of pyrrolo-[1,2,5]benzothiadiazepine were prepared and evaluated against Schistosoma japonica. The biological data revealed that most benzothiazepine derivatives show anti-schistosomal activity to some extent, while α-chloronation of the title compound and another bioisosteric derivative pyrrolo-[1,2,5]benzodiazepine displayed the most distinct worm killing activity. This study proved that benzodiazepine may serve as a novel structural skeleton for the development of anti-schistosomal agents.

Anthelmintic Activity of the Natural Compound (+)-Limonene Epoxide against Schistosoma mansoni

Blood fluke of the genus Schistosoma are the etiological agents of human schistosomiasis, an important neglected tropical disease that afflicts over 200 million people worldwide. The treatment for this disease relies heavily on a single drug, praziquantel. Recent reports of praziquantel resistance raise concerns about future control of the disease and show the importance of developing new antischistosomal drugs. Currently, natural products have been a good source for drug development. (+)-Limonene epoxide is a mixture of cis and trans isomers found in many plants. Here, we report the in vitro effect of this natural compound on the survival time of Schistosoma mansoni adult worms. In addition, we examined alterations on the tegumental surface of adult schistosomes by means of confocal laser scanning microscopy. The effects of (+)-limonene epoxide at 25 µg/mL on S. mansoni adult worms were similar to those of the positive control (praziquantel), with reduction in motility and death of all worms after 120 h. Confocal laser scanning microscopy revealed that (+)-limonene epoxide-mediated worm killing was associated with tegumental destruction. Our results, along with the low toxicity of the (+)-limonene epoxide, suggest that this natural compound might be promising for the development of new schistosomicidal agents.