International Journal for Parasitology: Drugs and Drug Resistance最新文献

{"title":"Selenosugars targeting the infective stage of Trypanosoma brucei with high selectivity","authors":"Estefanía Dibello ,&nbsp;Natalia Oddone ,&nbsp;Jaime Franco ,&nbsp;Tünde-Zita Illyés ,&nbsp;Andrea Medeiros ,&nbsp;Attila Kiss ,&nbsp;Fanni Hőgye ,&nbsp;Katalin E. Kövér ,&nbsp;László Szilágyi ,&nbsp;Marcelo A. Comini","doi":"10.1016/j.ijpddr.2024.100529","DOIUrl":"10.1016/j.ijpddr.2024.100529","url":null,"abstract":"<div><p>Earlier evidences showed that diglycosyl diselenides are active against the infective stage of African trypanosomes (top hits IC₅₀ 0.5 and 1.5 μM) but poorly selective (selectivity index &lt;10). Here we extended the study to 33 new seleno-glycoconjugates with the aim to improve potency and selectivity. Three selenoglycosides and three glycosyl selenenylsulfides displayed IC₅₀ against bloodstream <em>Trypanosoma brucei</em> in the sub-μM range (IC₅₀ 0.35–0.77 μM) and four of them showed an improved selectivity (selectivity index &gt;38-folds <em>vs.</em> murine and human macrohages). For the glycosyl selenylsulfides, the anti-trypanosomal activity was not significantly influenced by the nature of the moiety attached to the sulfur atom. Except for a quinoline-, and to a minor extent a nitro-derivative, the most selective hits induced a rapid (within 60 min) and marked perturbation of the LMWT-redox homeostasis. The formation of selenenylsulfide glycoconjugates with free thiols has been identified as a potential mechanism involved in this process.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"24 ","pages":"Article 100529"},"PeriodicalIF":4.0,"publicationDate":"2024-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000101/pdfft?md5=ab48ca5469710be897ae174f49a0ce29&pid=1-s2.0-S2211320724000101-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140025750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modified peptides and organic metabolites of cyanobacterial origin with antiplasmodial properties","authors":"Maria Elizbeth Alvarez-Sánchez ,&nbsp;Rodrigo Arreola ,&nbsp;Saray Quintero-Fabián ,&nbsp;Gilberto Pérez-Sánchez","doi":"10.1016/j.ijpddr.2024.100530","DOIUrl":"10.1016/j.ijpddr.2024.100530","url":null,"abstract":"<div><p>As etiological agents of malaria disease, <em>Plasmodium</em> spp. parasites are responsible for one of the most severe global health problems occurring in tropical regions of the world. This work involved compiling marine cyanobacteria metabolites reported in the scientific literature that exhibit antiplasmodial activity. Out of the 111 compounds mined and 106 tested, two showed antiplasmodial activity at very low concentrations, with IC₅₀ at 0.1 and 1.5 nM (peptides: dolastatin 10 and lyngbyabellin A, 1.9% of total tested). Examples of chemical derivatives generated from natural cyanobacterial compounds to enhance antiplasmodial activity and <em>Plasmodium</em> selectivity can be found in successful findings from nostocarboline, eudistomin, and carmaphycin derivatives, while bastimolide derivatives have not yet been found. Overall, 57% of the reviewed compounds are peptides with modified residues producing interesting active moieties, such as α- and β-epoxyketone in camaphycins. The remaining compounds belong to diverse chemical groups such as alkaloids, macrolides, polycyclic compounds, and halogenated compounds. The Dolastatin 10 and lyngbyabellin A, compounds with antiplasmodial high activity, are cytoskeletal disruptors with different protein targets<strong>.</strong></p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"24 ","pages":"Article 100530"},"PeriodicalIF":4.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000113/pdfft?md5=9a49b895613b1eab84beb9f9a6b66ff0&pid=1-s2.0-S2211320724000113-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140025402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revisiting anthelmintic resistance in sheep flocks from São Paulo State, Brazil","authors":"Cesar C. Bassetto ,&nbsp;Ana Cláudia A. Albuquerque ,&nbsp;José Gabriel G. Lins ,&nbsp;Naiara M. Marinho-Silva ,&nbsp;Marianna L.E. Chocobar ,&nbsp;Hornblenda J.S. Bello ,&nbsp;Mateus O. Mena ,&nbsp;Simone C.M. Niciura ,&nbsp;Alessandro F.T. Amarante ,&nbsp;Ana Carolina S. Chagas","doi":"10.1016/j.ijpddr.2024.100527","DOIUrl":"10.1016/j.ijpddr.2024.100527","url":null,"abstract":"<div><p><em>Haemonchus contortus</em> and <em>Trichostrongylus colubriformis</em> are the most important gastrointestinal nematodes causing serious losses in sheep production of tropical and subtropical regions. Prophylaxis of gastrointestinal nematode infections is based on anthelmintics use, but their frequent administration selects multiple-resistant parasites. To evaluate how the situation has changed over the last decades, the anthelmintic resistance status of gastrointestinal nematodes in sheep flocks was assessed in the current study and compared to previous surveys. In each one of the 15 flocks evaluated, animals (n ≥ 7) were allocated into at least five groups and treated as follows: 1) untreated control; 2) albendazole; 3) levamisole; 4) ivermectin; and 5) monepantel. If more animals were available, two additional groups were included: 6) closantel, and 7) moxidectin. The faecal egg count reduction test (FECRT) was carried out to evaluate the pre- and post-treatment using the SHINY tool. <em>Haemonchus</em> spp. was the most prevalent nematode from faecal cultures. The mean efficacy of albendazole was 40%. Only in two farms, levamisole presented a relatively high percentage of reduction in the FECRT about 90%, while ivermectin and moxidectin presented the worst mean efficacy of 34% and 21% among all farms, respectively. Like other anthelmintics, closantel demonstrated low efficacy (63%) across all farms evaluated. Monepantel presented an overall mean efficacy of 79%, but it was the only anthelmintic that presented efficacy ≥95%, in five farms. The results revealed that gastrointestinal nematodes with multiple anthelmintic resistance were prevalent in all 15 sheep herds. The research suggests that nematodes are becoming more and more resistant to various anthelmintic compounds, which has made the problem worse. This circumstance highlights the necessity to put into practice sustainable and long-lasting methods to prevent gastrointestinal nematode infections in sheep husbandry.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"24 ","pages":"Article 100527"},"PeriodicalIF":4.0,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000083/pdfft?md5=af6aef33db2a09fa18a2f4db9ed5aaad&pid=1-s2.0-S2211320724000083-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140025393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The first report of triple anthelmintic resistance on a French Thoroughbred stud farm","authors":"Aurélie Merlin ,&nbsp;Nicolas Larcher ,&nbsp;José-Carlos Vallé-Casuso","doi":"10.1016/j.ijpddr.2024.100528","DOIUrl":"10.1016/j.ijpddr.2024.100528","url":null,"abstract":"<div><p>This study assessed the anthelmintic resistance in strongylid nematodes against commonly used anthelmintic (AH) drugs in a French galloping racehorse stud farm from March to December 2023. Faecal egg count reduction tests (FECRTs) were conducted in three different groups of Thoroughbred yearlings (a group of 6 males, a group of 13 females and a group of 8 females and 3 males) following the new World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines. The efficacy of fenbendazole was tested in two groups once during the monitoring period (in March), the efficacy of ivermectin in 3 groups twice (in March–April and in November–December) and the efficacy of pyrantel in one group once (in May–June). For each FECRT, the 90% confidence interval of the percentage faecal egg count reduction was calculated using the hybrid Frequentist/Bayesian analysis method. The resistance in strongylids was observed to fenbendazole, pyrantel and ivermectin in all the groups in which these drugs were tested. The number of animals in each group was sufficient to reach ≥80% power for the resistance test. The results highlight the first case of triple AH resistance in strongylids in France. Further studies involving more farms and equids are required to assess the prevalence of AH resistance in France and refine recommendations for owners.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"24 ","pages":"Article 100528"},"PeriodicalIF":4.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000095/pdfft?md5=71a9a58a02e2da5306d66c1f63d74264&pid=1-s2.0-S2211320724000095-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139948166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated application of transcriptomics and metabolomics provides insight into the mechanism of Eimeria tenella resistance to maduramycin","authors":"Huanzhi Zhao ,&nbsp;Hui Dong ,&nbsp;Qiping Zhao,&nbsp;Shunhai Zhu,&nbsp;Liushu Jia,&nbsp;Sishi Zhang,&nbsp;Qian Feng,&nbsp;Yu Yu,&nbsp;Jinwen Wang,&nbsp;Bing Huang,&nbsp;Hongyu Han","doi":"10.1016/j.ijpddr.2024.100526","DOIUrl":"10.1016/j.ijpddr.2024.100526","url":null,"abstract":"<div><p>Avian coccidiosis, caused by <em>Eimeria</em> parasites, continues to devastate the poultry industry and results in significant economic losses. Ionophore coccidiostats, such as maduramycin and monensin, are widely used for prophylaxis of coccidiosis in poultry. Nevertheless, their efficacy has been challenged by widespread drug resistance. However, the underlying mechanisms have not been revealed. Understanding the targets and resistance mechanisms to anticoccidials is critical to combat this major parasitic disease. In the present study, maduramycin-resistant (MRR) and drug-sensitive (DS) sporozoites of <em>Eimeria tenella</em> were purified for transcriptomic and metabolomic analysis. The transcriptome analysis revealed 5016 differentially expressed genes (DEGs) in MRR compared to DS, and KEGG pathway enrichment analysis indicated that DEGs were involved in spliceosome, carbon metabolism, glycolysis, and biosynthesis of amino acids. In the untargeted metabolomics assay, 297 differentially expressed metabolites (DEMs) were identified in MRR compared to DS, and KEGG pathway enrichment analysis indicated that these DEMs were involved in 10 pathways, including fructose and mannose metabolism, cysteine and methionine metabolism, arginine and proline metabolism, and glutathione metabolism. Targeted metabolomic analysis revealed 14 DEMs in MRR compared to DS, and KEGG pathway analysis indicated that these DEMs were involved in 20 pathways, including fructose and mannose metabolism, glycolysis/gluconeogenesis, and carbon metabolism. Compared to DS, energy homeostasis and amino acid metabolism were differentially regulated in MRR. Our results provide gene and metabolite expression landscapes of <em>E. tenella</em> following maduramycin induction. This study is the first work involving integrated transcriptomic and metabolomic analyses to identify the key pathways to understand the molecular and metabolic mechanisms underlying drug resistance to polyether ionophores in coccidia.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"24 ","pages":"Article 100526"},"PeriodicalIF":4.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000071/pdfft?md5=d8edf8f2af5c175329465835ce3f57b0&pid=1-s2.0-S2211320724000071-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139821578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of the treatment using a microemulsion loaded with epoxy-α-lapachone in combination with meglumine antimoniate against murine infection by Leishmania (Leishmania) amazonensis","authors":"Juliana Figueiredo Peixoto ,&nbsp;Luiz Filipe Gonçalves-Oliveira ,&nbsp;Franklin Souza-Silva ,&nbsp;Luzia Monteiro de Castro Côrtes ,&nbsp;Léa Cysne Finkelstein ,&nbsp;Geovane Dias-Lopes ,&nbsp;Beatriz Ferreira de Carvalho Patricio ,&nbsp;Carolina Guimarães de Souza Lima ,&nbsp;Helvécio Vinícius Antunes Rocha ,&nbsp;Fernando de Carvalho da Silva ,&nbsp;Vitor Francisco Ferreira ,&nbsp;Bernardo Acácio Santini Pereira ,&nbsp;Carlos Roberto Alves","doi":"10.1016/j.ijpddr.2024.100525","DOIUrl":"https://doi.org/10.1016/j.ijpddr.2024.100525","url":null,"abstract":"<div><p>Leishmaniasis is a disease caused by <em>Leishmania</em> spp., affecting millions of people around the world. For decades, its treatment has been based on pentavalent antimonials, which notoriously cause toxic side effects in patients. In this study, epoxy-α-lapachone incorporated into an oil-in-water-type microemulsion (ELAP-ME) and meglumine antimoniate (MA) were assayed in monotherapy and in combination (ELAP-ME/MA) in BALB/c mice infected with <em>Leishmania</em> (<em>Leishmania</em>) <em>amazonensis</em>. In general, there was a reduction in paw lesion size (up to 37% reduction) and decreases of parasite loads in the footpad (∼40%) and lymph nodes (∼31%) of animals treated with ELAP-ME/MA, when compared to the non-treated control groups. Analyses of serum biochemical parameters revealed that the ELAP-ME/MA showed lower renal and hepatic toxicity when compared to MA 2-doses/week monotherapy. These findings indicate that the ELAP-ME/MA combination may be a promising approach for the treatment of cutaneous leishmaniasis.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"24 ","pages":"Article 100525"},"PeriodicalIF":4.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S221132072400006X/pdfft?md5=b6325d66766d45e757e6de8aef6c679c&pid=1-s2.0-S221132072400006X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139731925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chicory (Cichorium intybus) reduces cyathostomin egg excretion and larval development in grazing horses","authors":"Joshua Malsa ,&nbsp;Leslie Boudesocque-Delaye ,&nbsp;Laurence Wimel ,&nbsp;Juliette Auclair-Ronzaud ,&nbsp;Bertrand Dumont ,&nbsp;Núria Mach ,&nbsp;Fabrice Reigner ,&nbsp;Fabrice Guégnard ,&nbsp;Angélique Chereau ,&nbsp;Delphine Serreau ,&nbsp;Isabelle Théry-Koné ,&nbsp;Guillaume Sallé ,&nbsp;Géraldine Fleurance","doi":"10.1016/j.ijpddr.2024.100523","DOIUrl":"10.1016/j.ijpddr.2024.100523","url":null,"abstract":"<div><p>Cyathostomins are the most prevalent parasitic nematodes of grazing horses. They are responsible for colic and diarrhea in their hosts. After several decades of exposure to synthetic anthelmintics, they have evolved to become resistant to most compounds. In addition, the drug-associated environmental side-effects question their use in the field. Alternative control strategies, like bioactive forages, are needed to face these challenges. Among these, chicory (<em>Cichorium intybus,</em> Puna II cultivar (cv.)) is known to convey anthelmintic compounds and may control cyathostomins in grazing horses. To challenge this hypothesis, we measured fecal egg counts and the rate of larval development in 20 naturally infected young saddle horses (2-year-old) grazing either (i) a pasture sown with chicory (n = 10) or (ii) a mesophile grassland (n = 10) at the same stocking rate (2.4 livestock unit (LU)/ha). The grazing period lasted 45 days to prevent horse reinfection. Horses in the chicory group mostly grazed chicory (89% of the bites), while those of the control group grazed mainly grasses (73%). Cyathostomins egg excretion decreased in both groups throughout the experiment. Accounting for this trajectory, the fecal egg count reduction (FECR) measured in individuals grazing chicory relative to control individuals increased from 72.9% at day 16 to 85.5% at the end of the study. In addition, larval development in feces from horses grazed on chicory was reduced by more than 60% from d31 compared to control individuals. Using a metabarcoding approach, we also evidenced a significant decrease in cyathostomin species abundance in horses grazing chicory. Chicory extract enriched in sesquiterpenes lactones was tested on two cyathostomins isolates. The estimated IC₅₀ was high (1 and 3.4 mg/ml) and varied according to the pyrantel sensitivity status of the worm isolate. We conclude that the grazing of chicory (cv. Puna II) by horses is a promising strategy for reducing cyathostomin egg excretion and larval development that may contribute to lower the reliance on synthetic anthelmintics. The underpinning modes of action remain to be explored further.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"24 ","pages":"Article 100523"},"PeriodicalIF":4.0,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000046/pdfft?md5=2bec70aff57f7308fa3ded6553ccdc49&pid=1-s2.0-S2211320724000046-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139829774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional validation of novel levamisole resistance marker S168T in Haemonchus contortus","authors":"Alistair Antonopoulos ,&nbsp;Claude L. Charvet ,&nbsp;Kirsty Maitland ,&nbsp;Stephen R. Doyle ,&nbsp;Cédric Neveu ,&nbsp;Roz Laing","doi":"10.1016/j.ijpddr.2024.100524","DOIUrl":"https://doi.org/10.1016/j.ijpddr.2024.100524","url":null,"abstract":"<div><p>Recently, a S168T variant in the acetylcholine receptor subunit ACR-8 was associated with levamisole resistance in the parasitic helminth <em>Haemonchus contortus</em>. Here, we used the <em>Xenopus laevis</em> oocyte expression system and two-electrode voltage-clamp electrophysiology to measure the functional impact of this S168T variant on the <em>H. contortus</em> levamisole-sensitive acetylcholine receptor, L-AChR-1.1. Expression of the ACR-8 S168T variant significantly reduced the current amplitude elicited by levamisole compared to acetylcholine, with levamisole changing from a full to partial agonist on the recombinant L-AChR. Functional validation of the S168T mutation on modulating levamisole activity at the receptor level highlights its critical importance as both a mechanism and a marker of levamisole resistance.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"24 ","pages":"Article 100524"},"PeriodicalIF":4.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000058/pdfft?md5=1b21aa8c04868e8301cc6aeb6eb256fb&pid=1-s2.0-S2211320724000058-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139718696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-activity relationship and target investigation of 2-aryl quinolines with nematocidal activity","authors":"Harrison T. Shanley ,&nbsp;Aya C. Taki ,&nbsp;Nghi Nguyen ,&nbsp;Tao Wang ,&nbsp;Joseph J. Byrne ,&nbsp;Ching-Seng Ang ,&nbsp;Michael G. Leeming ,&nbsp;Shuai Nie ,&nbsp;Nicholas Williamson ,&nbsp;Yuanting Zheng ,&nbsp;Neil D. Young ,&nbsp;Pasi K. Korhonen ,&nbsp;Andreas Hofmann ,&nbsp;Bill C.H. Chang ,&nbsp;Tim N.C. Wells ,&nbsp;Cécile Häberli ,&nbsp;Jennifer Keiser ,&nbsp;Abdul Jabbar ,&nbsp;Brad E. Sleebs ,&nbsp;Robin B. Gasser","doi":"10.1016/j.ijpddr.2024.100522","DOIUrl":"10.1016/j.ijpddr.2024.100522","url":null,"abstract":"<div><p>Within the context of our anthelmintic discovery program, we recently identified and evaluated a quinoline derivative, called ABX464 or obefazimod, as a nematocidal candidate; synthesised a series of analogues which were assessed for activity against the free-living nematode <em>Caenorhabditis elegans</em>; and predicted compound-target relationships by thermal proteome profiling (TPP) and <em>in silico</em> docking. Here, we logically extended this work and critically evaluated the anthelmintic activity of ABX464 analogues on <em>Haemonchus contortus</em> (barber's pole worm) – a highly pathogenic nematode of ruminant livestock. First, we tested a series of 44 analogues on <em>H. contortus</em> (larvae and adults) to investigate the nematocidal pharmacophore of ABX464, and identified one compound with greater potency than the parent compound and showed moderate activity against a select number of other parasitic nematodes (including <em>Ancylostoma, Heligmosomoides</em> and <em>Strongyloides</em> species). Using TPP and <em>in silico</em> modelling studies, we predicted protein HCON_00074590 (a predicted aldo-keto reductase) as a target candidate for ABX464 in <em>H. contortus</em>. Future work aims to optimise this compound as a nematocidal candidate and investigate its pharmacokinetic properties. Overall, this study presents a first step toward the development of a new nematocide.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"24 ","pages":"Article 100522"},"PeriodicalIF":4.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000034/pdfft?md5=256699c4f264c5754a968fc968bc1efd&pid=1-s2.0-S2211320724000034-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139560631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herbal-based compounds: A review on treatments of cryptosporidiosis","authors":"Fatemeh Namazi,&nbsp;Seyed Mostafa Razavi","doi":"10.1016/j.ijpddr.2024.100521","DOIUrl":"10.1016/j.ijpddr.2024.100521","url":null,"abstract":"<div><p>Cryptosporidium, a monoxenous apicomplexan coccidia, is a prevalent diarrhetic and an opportunistic agent, mainly in immunocompromised individuals. As there are few chemotherapeutic compounds that have limited efficacy, we need to identify new compounds or specific parasite targets for designing more potent drugs to treat cryptosporidiosis. Herbal products with low toxicity, environmental compatibility, wide therapeutic potential, and abundant resources can be considered alternatives for treatment. The current review tried to summarize the studies on plants or herbal bioactive constituents with anti-cryptosporidial activities. Based on constituents, plants act via different mechanisms, and further investigations are needed to clarify the exact mechanisms by which they act on the developmental stages of the parasite or host-parasite relationships.</p></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"24 ","pages":"Article 100521"},"PeriodicalIF":4.0,"publicationDate":"2024-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2211320724000022/pdfft?md5=ff71ee0b4ab1b379ab28bda06662f398&pid=1-s2.0-S2211320724000022-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139498237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}