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

{"title":"Tartrolon E rapidly blocks Toxoplasma gondii capacity to invade host cells","authors":"Fernanda G. Fumuso ,&nbsp;Jason A. Clement ,&nbsp;Matthew J. Todd ,&nbsp;Roberta M. O'Connor","doi":"10.1016/j.ijpddr.2025.100591","DOIUrl":"10.1016/j.ijpddr.2025.100591","url":null,"abstract":"<div><div>Toxoplasmosis is a worldwide parasitic disease caused by the apicomplexan <em>Toxoplasma gondii</em>. Severe neurological illness occurs in immunosuppressed patients, and congenital disorders can follow transplacental primo infection during pregnancy. New effective antiparasitic drugs are needed since chronic cystic stages are resistant to current available treatments, and some of the congenital infections are unresponsive to available therapeutics. Tartrolon E (trtE) is a marine secondary metabolite that has high selectivity against human and animal apicomplexan parasites including <em>T. gondii</em>, <em>Cryptosporidium parvum</em> and <em>Plasmodium falciparum</em>. We evaluated the effect of the compound on extracellular tachyzoite viability, morphology, membrane permeability and its ability to block host cell attachment and/or invasion. While 80 % of <em>T. gondii</em> infective capacity is blocked after only 30 min of compound treatment, parasite viability, morphology, membrane integrity and host cell attachment were unaffected until after 4 h of treatment. These effects were irreversible when parasites were allowed to infect host cells after trtE treatment. Drug exposure for more than 4 h significantly affected tachyzoite survival and altered parasite morphology. The mechanism of action of trtE is still unknown but includes blocking parasite invasion processes. Further research is needed to determine the molecular target of trtE to further progress the compound as an antiparasitic candidate.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100591"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143830062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic, in-silico and in vitro studies with nitrofurans reveal potent leishmanicidal activity and inhibition of trypanothione reductase","authors":"Julia Andrés-Rodríguez ,&nbsp;María-Cristina González-Montero ,&nbsp;Nerea García-Fernández ,&nbsp;Juan-José Galano-Frutos ,&nbsp;Maria-Cristina de Rosa ,&nbsp;Patricia Ferreira ,&nbsp;María-Yolanda Pérez-Pertejo ,&nbsp;Rosa M. Reguera ,&nbsp;Rafael Balaña-Fouce ,&nbsp;Carlos García-Estrada","doi":"10.1016/j.ijpddr.2025.100605","DOIUrl":"10.1016/j.ijpddr.2025.100605","url":null,"abstract":"<div><div>Visceral leishmaniasis caused by <em>Leishmania infantum</em> and <em>Leishmania donovani</em> is one of the neglected tropical diseases (NTDs) caused by trypanosomatids with treatment options limited to outdated drugs often causing adverse effects and promoting drug resistance. Previous antileishmanial drug discovery campaigns have identified nitroheterocyclic molecules with high efficacy and a high selectivity index. Therefore, we have evaluated on our screening platform of fluorescent <em>L. donovani</em> amastigotes, the antileishmanial activity of seven nitrofuran derivatives: furazolidone, nitrofurazone, nitrofurantoin, nifurtimox, 5-nitro-2-furaldehyde diacetate, PYZD-4409 and 5-nitro-2-furonitrile. These compounds showed good efficacy against axenic and intramacrophage amastigotes, most of them showing low cytotoxicity in mammalian cell lines. These nitrofuran derivatives induced reactive oxygen species production in axenic amastigotes and inhibited trypanothione reductase (TryR) either in uncompetitive or competitive manner, thus suggesting that their mechanism of action involves increased oxidative stress caused by an imbalance in redox metabolism. Furazolidone exhibited the most promising antileishmanial profile, and molecular docking analysis revealed consistency with the strongest TryR uncompetitive inhibitory effect, demonstrating its high affinity for an alternative binding site near the substrate (oxidized trypanothione) pocket. Docking results also highlighted PYZD-4409 as the compound with the highest binding affinity, and showed consistency with its competitive inhibition mechanism. Furthermore, similar binding modes identified across <em>L. donovani</em> TryR and other homologous proteins suggest the potential broad-spectrum activity of these nitrofuran derivatives, thus underscoring their importance as promising candidates for the development of novel antileishmanial therapies with broad-spectrum applications.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100605"},"PeriodicalIF":3.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144772517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resistance to apicoplast translational inhibitors in Plasmodium","authors":"Jessica L. Home,&nbsp;Geoffrey I. McFadden,&nbsp;Christopher D. Goodman","doi":"10.1016/j.ijpddr.2025.100597","DOIUrl":"10.1016/j.ijpddr.2025.100597","url":null,"abstract":"<div><div>The spread of drug-resistant <em>Plasmodium</em> threatens malaria control efforts. Thus, understanding the mechanisms of resistance is crucial for implementing effective treatments and prevention strategies. The prokaryote-like translational machinery encoded by the apicoplast is the apparent target of several antibiotics with antimalarial activity. Among them, doxycycline and clindamycin are widely used for malaria treatment and/or chemoprophylaxis. However, the mechanisms underlying <em>Plasmodium</em> resistance to apicoplast-targeting antibiotics, and the evolution of such resistance mechanisms, remain largely unknown. In this review, we summarise reported cases of resistance to apicoplast translational inhibitors uncovered in either laboratory or clinical settings. We highlight the potential evolutionary pathway of doxycycline resistance, explore why resistance to these antibiotics remains rare in the field, and assess whether expanding their use in malaria treatment and prevention is a viable strategy.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100597"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimalarial drug resistance and drug discovery: learning from the past to innovate the future","authors":"Liana Theodoridis,&nbsp;Teresa G. Carvalho","doi":"10.1016/j.ijpddr.2025.100602","DOIUrl":"10.1016/j.ijpddr.2025.100602","url":null,"abstract":"<div><div>The emergence and spread of artemisinin-resistant malaria over the past 15 years has led to a recent rise in global malaria cases and represents a major public health concern. Following decades of intense research efforts, the first malaria vaccine has been approved for clinical use in October of 2021. However, its 36 % efficacy highlights the ongoing need for novel and effective drugs to combat malaria. The majority of current antimalarials are derivatives of previous efficient compounds whilst new treatments with diverse chemical scaffolds have not been implemented into clinical practice since 1996. We argue that current research efforts should focus on developing novel chemical classes of compounds to help fight drug resistant malaria. Here we provide a comprehensive review of the antimalarial treatments currently in clinical use and discuss their significant limitations due to parasite drug resistance. Further, we discuss various approaches to antimalarial drug discovery and offer new perspectives on the topic, informing on current methods, both rarely and extensively used. Collating the most recent and up-to-date drug discovery strategies will not only maximise current global research efforts but will ensure all possible drug development avenues are trialed. This review provides innovative insights to circumvent antimalarial drug resistance and diversify malaria therapeutics.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"28 ","pages":"Article 100602"},"PeriodicalIF":4.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144653272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased activity of CF3-derivatized levamisole at the ACC-2 receptor from the parasitic nematode Haemonchus contortus","authors":"Autumn Collins ,&nbsp;Sierra Varley ,&nbsp;Tobias Clark ,&nbsp;Nathan Chubb ,&nbsp;Sean Forrester ,&nbsp;Jean-Paul Desaulniers","doi":"10.1016/j.ijpddr.2025.100587","DOIUrl":"10.1016/j.ijpddr.2025.100587","url":null,"abstract":"<div><div>The acetylcholine-gated chloride channel (ACC) family in parasitic nematodes represents a promising target for anthelmintic drug development. Levamisole, a widely known and utilized cholinergic agonist, has been used for decades to address many types of parasitic infections by targeting nematode nicotinic acetylcholine receptors (nAChRs) in nematodes. In this study, we report the synthesis and pharmacological evaluation of eight levamisole derivatives, five of which are novel, on the <em>H. contortus</em> ACC-2 receptor. This includes a CF₃-derivatized compound we have identified as compound <strong>6</strong> whose structure contains levamisole as a backbone with the addition of a 2-trifluoromethyl benzyl group. Electrophysiological assays revealed that compound <strong>6</strong> exhibited a five-fold increase in sensitivity (EC₅₀ 20 μM) compared to levamisole (EC₅₀ 100 μM), our parent compound, with an EC₅₀ comparable to that of acetylcholine (20 μM). Investigation of the <em>in silico</em> docking of compound <strong>6</strong> with <em>H. contortus</em> ACC-2 suggest that it interacts uniquely within the <em>H. contortus</em> ACC-2 binding pocket, which may contribute to its increased receptor sensitivity. These findings highlight the potential of structural modifications containing an electron-withdrawing group at the 2-position which can significantly enhance activity at the <em>H. contortus</em> ACC-2 receptor. This opens many avenues for the development of more effective treatments against parasitic nematodes, in an environment with increasing resistance.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100587"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562769","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":"Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injury","authors":"Jing-Mei Lu ,&nbsp;Guang-Nan Jin ,&nbsp;Yan Xin ,&nbsp;Jing-Wen Ma ,&nbsp;Xin-Yu Shen ,&nbsp;Yan-Zhu Quan ,&nbsp;Yi-Ming Liu ,&nbsp;Jin-Yi Zhou ,&nbsp;Bing-Zhe Wang ,&nbsp;Ying-Biao Li ,&nbsp;Xiang Xu ,&nbsp;Lian-Xun Piao","doi":"10.1016/j.ijpddr.2024.100575","DOIUrl":"10.1016/j.ijpddr.2024.100575","url":null,"abstract":"<div><div><em>Toxoplasma gondii</em>, a neurotropic protozoan parasite, affects the central nervous system and causes various neurological disorders. Previous studies have demonstrated that Arctigenin (AG) exhibits anti-<em>T. gondii</em> activity and reduces depression-like behaviors induced by <em>T. gondii</em> infection. This study aimed to enhance AG's brain-targeting and therapeutic efficacy by developing lactoferrin-modified nanoemulsions loaded with AG (Lf-AG-NEs). Lf-modified nanoemulsions were prepared and assessed using <em>in vivo</em> and <em>in vitro</em> infection models with the <em>T. gondii</em> RH strain, and a co-culture system of BV2 microglia and primary neuron cells. The effects of Lf-AG-NEs on <em>T. gondii</em>-induced neuronal injury were examined, and potential molecular mechanisms were elucidated through real-time quantitative PCR, western blotting, immunofluorescence, flow cytometry, immunohistochemistry, and Nissl staining. <em>In vitro</em> assessments showed significant increases in cellular uptake and blood-brain barrier penetration by Lf-AG-NEs. These nanoemulsions notably inhibited <em>T. gondii</em> proliferation in brain tissue and BV2 cells, surpassing the effects of free AG or AG-NEs alone. Additionally, Lf-AG-NEs substantially alleviated neuropathological changes and reduced microglial activation and neuroinflammation by downregulating the TLR4/NF-κB and TNFR1/NF-κB signaling pathways. Co-culturing BV2 cells with primary cortical neurons indicated that Lf-AG-NEs, similarly to CLI-095 and R7050, attenuated <em>T. gondii</em>-induced microglial activation and subsequent neuronal injury. In conclusion, the successfully prepared Lf-AG-NEs not only enhanced the anti-<em>T. gondii</em> effect but also strengthened the protective impact against neuronal injury induced by <em>T. gondii</em>, through the modulation of microglial signaling pathways.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100575"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893987","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":"Combining the zebrafish embryo developmental toxicity assay (ZEDTA) with hemoglobin staining to accelerate the research of novel antimalarial drugs for pregnant women","authors":"Lucia Borrallo-Lopez ,&nbsp;Laura Guzman ,&nbsp;Noelia G. Romero ,&nbsp;Anna Sampietro ,&nbsp;Ana Mallo-Abreu ,&nbsp;Laia Guardia-Escote ,&nbsp;Elisabet Teixidó ,&nbsp;Burkhard Flick ,&nbsp;Xavier Fernàndez-Busquets ,&nbsp;Diego Muñoz-Torrero ,&nbsp;Marta Barenys","doi":"10.1016/j.ijpddr.2025.100582","DOIUrl":"10.1016/j.ijpddr.2025.100582","url":null,"abstract":"<div><h3>Background</h3><div>Malaria during pregnancy implies a high risk for the mother and the developing child. However, the therapeutic options for pregnant women have historically been very limited, especially during the first trimester of pregnancy due to potential adverse effects on embryo-fetal development. Recently, there has been great controversy regarding these potential embryo-fetal adverse effects because the results of rodent studies were not in accordance with the clinical data available, and finally the WHO has changed the recommendations for pregnant women with uncomplicated <em>P. falciparum</em> malaria to treatment with artemether-lumefantrine during the first trimester. The discrepancy between pre-clinical and clinical studies has been attributed to species-differences in the duration of the window of susceptibility of circulating primitive erythroblasts.</div></div><div><h3>Methods</h3><div>Here we provide a tool based on an alternative method to animal experimentation that accelerates the research of novel drugs for pregnant women. We have adapted the zebrafish embryo developmental toxicity assay to include hemoglobin staining in the embryos and two time-points of lethality and dysmorphogenesis evaluation. These two time-points were selected to include one when the development is independent of and one when the development is dependent of erythrocytes function. The method was used to test four marketed antimalarial drugs and three new antimalarial drug candidates.</div></div><div><h3>Results</h3><div>Our combination of tests can correctly predict the teratogenic and non-teratogenic effects of several antimalarial marketed drugs (artemisinin, quinine, chloroquine, and dihydroartemisinin + desbutyl-lumefantrine). Furthermore, we have tested three new drug candidates (GS-GUAN, DONE3TCl, and YAT2150) with novel mechanisms of action, and different from those of the marketed antimalarial drugs.</div></div><div><h3>Conclusions</h3><div>We propose a decision tree combining the results of the two time-points of evaluation together with the information on significant erythrocyte depletion. The aim of this decision tree is to identify compounds with no or lower hazard on teratogenicity or erythrocyte depletion at an early phase of the drug development process.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100582"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070871","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":"Quantitative DNA metabarcoding reveals species composition of a macrocyclic lactone and pyrantel resistant cyathostomin population in the UK","authors":"K.E. Bull ,&nbsp;J. Hodgkinson ,&nbsp;K. Allen ,&nbsp;J. Poissant ,&nbsp;L.E. Peachey","doi":"10.1016/j.ijpddr.2024.100576","DOIUrl":"10.1016/j.ijpddr.2024.100576","url":null,"abstract":"<div><div>Cyathostomins are the most abundant equid endoparasites globally. There are approximately fifty cyathostomin species and, whilst they occupy distinct niches within the large intestine, they are generally considered to share similar characteristics in terms of pathogenicity and response to drug treatment. There are three classes of anthelmintic licensed in the UK to treat cyathostomins (benzimidazoles, tetrahydropyrimidines and macrocyclic lactones) and cases of resistance have been documented for all classes. Previously, faecal egg count reduction tests (FECRT) on four UK Thoroughbred studs revealed multidrug resistant cyathostomins on one stud (A), with evidence of resistance to the macrocyclic lactones (MLs) ivermectin (IVM) and moxidectin (MOX), and to pyrantel (PYR). The remaining three studs (B-D) lacked resistance to IVM and MOX but had a shortened egg reappearance period post treatment.</div><div>To determine whether specific species could be associated with the observed resistance and shortened egg reappearance period, strongyle eggs collected from between six and 15 individual horses per stud were copro-cultured to third larval stage (L3), before and after anthelmintic treatment, over a three-year timeframe (2021–2023). Quantitative DNA metabarcoding of the ITS-2 region was carried out on all samples.</div><div>On stud A, single but differing species were found to be responsible for ML and pyrantel resistance in yearlings, <em>Cyathostomum catinatum</em> and <em>Cylicocyclus nassatus,</em> respectively. On studs B-D, with shortened egg reappearance periods, species composition remained largely unchanged post treatment.</div><div>This study is the first to quantitatively profile cyathostomin species composition pre- and post-treatment in a multidrug resistant population in the UK, revealing that resistance in cyathostomins was species specific. This raises the question of whether these species may be responsible for ML and PYR resistance more widely and indicates that anthelmintic resistance in cyathostomins may not be a multi-species phenomenon.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100576"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948410","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":"Selective activity of Tabebuia avellanedae against Giardia duodenalis infecting organoid-derived human gastrointestinal epithelia","authors":"Giulia Rigamonti ,&nbsp;Fabrizia Veronesi ,&nbsp;Elisabetta Chiaradia ,&nbsp;Petra Gosten-Heinrich ,&nbsp;Antonia Müller ,&nbsp;Leonardo Brustenga ,&nbsp;Stefano de Angelis ,&nbsp;Alessia Tognoloni ,&nbsp;Riccardo De Santo ,&nbsp;Christian Klotz ,&nbsp;Marco Lalle","doi":"10.1016/j.ijpddr.2025.100583","DOIUrl":"10.1016/j.ijpddr.2025.100583","url":null,"abstract":"<div><div><em>Giardia duodenalis</em> is a widespread intestinal protozoan that affects mammals, including humans. Symptoms can range from being subclinical to causing severe abdominal pain and diarrhoea. Giardiasis often requires repeated treatment with synthetic drugs like metronidazole. In recent years, treatment failures in clinical cases involving nitroimidazoles have been increasingly reported. Consequently, identifying therapeutic alternatives is necessary. Medicinal plants have traditionally been used as antiparasitic compounds, but systematic evaluation under controlled experimental conditions is often lacking. Here, we evaluated the <em>in vitro</em> efficacy of <em>Tabebuia avellanedae</em> dry and hydroalcoholic extracts, as well as one of its active compounds, β-lapachone, as potential treatment against <em>G. duodenalis</em> infection. We observed effective antigiardial activity for all tested compounds, with β-lapachone exhibiting lower IC₅₀ values than metronidazole. Cytotoxic effects often limit therapeutic concentration windows of opportunity, and choosing an informative model to assess them is not straightforward. In the present case, only <em>T. avellanedae</em> hydroalcoholic extract showed no cytotoxicity on tumoral human intestinal Caco-2 cell line, and only a trend of inhibition when tested on canine epithelial kidney MDCK cells. To introduce a more physiological test system, we used <em>in vitro G. duodenalis</em> infection experiments in a trans-well set-up using organoid derived monolayers (ODM) to assess at the same time drug efficacy against the parasite and safety on primary human intestinal epithelia, a likely surrogate for <em>in vivo</em> conditions. Our studies using this model point towards the potential therapeutic opportunity for non-systemic applications of <em>T. avellanedae</em> extracts and a relevant ingredient of these, β-lapachone. The data suggest that ODM co-cultures with <em>G. duodenalis</em> are suitable for testing antigiardial compounds, providing a more informative <em>in vitro</em> model before progressing to <em>in vivo</em> tests.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100583"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046545","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":"Biotransformation of anthelmintics in nematodes in relation to drug resistance","authors":"Ondřej Vosála ,&nbsp;Josef Krátký ,&nbsp;Petra Matoušková ,&nbsp;Nikola Rychlá ,&nbsp;Karolína Štěrbová ,&nbsp;Lucie Raisová Stuchlíková ,&nbsp;Ivan Vokřál ,&nbsp;Lenka Skálová","doi":"10.1016/j.ijpddr.2025.100579","DOIUrl":"10.1016/j.ijpddr.2025.100579","url":null,"abstract":"<div><div>In all organisms, the biotransformation of xenobiotics to less toxic and more hydrophilic compounds represents an effective defense strategy. In pathogens, the biotransformation of drugs (used for their elimination from the host) may provide undesirable protective effects that could potentially compromise the drug's efficacy. Accordingly, increased drug deactivation via accelerated biotransformation is now considered as one of the mechanisms of drug resistance. The present study summarizes the current knowledge regarding the biotransformation of anthelmintics, specifically drugs used to treat mainly nematodes, a group of parasites that are a significant health concern for humans and animals. The main biotransformation enzymes are introduced and their roles in anthelmintics metabolism in nematodes are discussed with a particular focus on their potential participation in drug resistance. Similarly, the inducibility of biotransformation enzymes with sublethal doses of anthelmintics is presented in view of its potential contribution to drug resistance development. In the conclusion, the main tasks awaiting scientists in this area are outlined.</div></div>","PeriodicalId":13775,"journal":{"name":"International Journal for Parasitology: Drugs and Drug Resistance","volume":"27 ","pages":"Article 100579"},"PeriodicalIF":4.1,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11787565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004891","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}