Molecular and biochemical parasitology最新文献

{"title":"Strategies for diagnosing Nosema bombycis (Microsporidia: Nosematidae); the agent of pebrine disease","authors":"Masoumeh Bagheri ,&nbsp;Shirin Dehghan ,&nbsp;Azadeh Zahmatkesh","doi":"10.1016/j.molbiopara.2024.111645","DOIUrl":"10.1016/j.molbiopara.2024.111645","url":null,"abstract":"<div><p>Pebrine disease, caused by <em>Nosema bombycis</em> (<em>N. bombycis</em>), is the most important pathogen known to the silk industry. Historical evidence from several countries shows that the outbreaks of pebrine disease have largely caused the decline of the sericulture industry. Prevention is the first line to combat pebrine as a deadly disease in silkworm; however, no effective treatment has yet been presented to treat the disease. Many different methods have been used for detection of pebrine disease agent. This review focuses on the explanation and comparison of these methods, and describes their advantages and/or disadvantages. Also, it highlights the ongoing advances in diagnostic methods for <em>N. bombycis</em> that could enable efforts to halt this microsporidia infection. The detection methods are categorized as microscopic, immunological and nucleic acid-based approaches, each with priorities over the other methods; however, the suitability of each method depends on the available equipment in the laboratory, the mass of infection, and the speed and sensitivity of detection. The accessibility and economic efficiency are compared as well as the speed and the sensitivity for each method. Although, the light microscopy is the most common method for detection of <em>N. bombycis</em>, qPCR is the most preferred method for large data based on speed and sensitivity as well as early detection ability.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pyridopyrimidinones as a new chemotype of calcium dependent protein kinase 1 (CDPK1) inhibitors for Cryptosporidium","authors":"Elise Waldron-Young ,&nbsp;Wissarut Wijitrmektong ,&nbsp;Ryan Choi ,&nbsp;Grant R. Whitman ,&nbsp;Matthew A. Hulverson ,&nbsp;Raheela Charania ,&nbsp;Aidan Keelaghan ,&nbsp;Li Li ,&nbsp;Songpol Srinual ,&nbsp;Sameer Nikhar ,&nbsp;Case W. McNamara ,&nbsp;Melissa S. Love ,&nbsp;Lauren Huerta ,&nbsp;Malina A. Bakowski ,&nbsp;Ming Hu ,&nbsp;Wesley C. Van Voorhis ,&nbsp;Jan R. Mead ,&nbsp;Gregory D. Cuny","doi":"10.1016/j.molbiopara.2024.111637","DOIUrl":"10.1016/j.molbiopara.2024.111637","url":null,"abstract":"<div><p>The protozoan protein kinase calcium-dependent protein kinase 1 (CDPK1) has emerged as a potential therapeutic target for the treatment of cryptosporidiosis. A focused screen of known kinase inhibitors identified a pyridopyrimidinone as a new chemotype of <em>Cryptosporidium parvum</em> (<em>Cp</em>) CDPK1 inhibitors. Structural comparison of <em>Cp</em>CDPK1 to two representative human kinases, RIPK2 and Src, revealed differences in the positioning of the αC-helix that was used in the design of a potent pyridopyrimidinone-based <em>Cp</em>CDPK1 inhibitor <strong>7</strong> (a.k.a. UH15–16, IC₅₀ = 10 nM), which blocked the growth of three <em>C. parvum</em> strains (EC₅₀ = 12–40 nM) as well as <em>C. hominis</em> (EC₅₀ = 85 nM) in HCT-8 host cells. Pharmacokinetic and tissue distribution analyses indicated that <strong>7</strong> had low systemic exposure after oral administration, but high gastrointestinal concentration, as well as good Caco-2 cell permeability. Finally, <strong>7</strong> demonstrated partial efficacy in an IL-12 knock-out mouse model of acute cryptosporidiosis.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNAs in opisthorchiids and their definitive hosts: Current Status and Perspectives","authors":"Xiang Li ,&nbsp;Jian Ding ,&nbsp;Xiaoli Zhang ,&nbsp;Xueli Zhang ,&nbsp;Xu Jiang ,&nbsp;Rui Chen ,&nbsp;Yang Cheng ,&nbsp;Yifan Sun ,&nbsp;Jie Wan ,&nbsp;Yu Zhang ,&nbsp;Jianping Cao ,&nbsp;Su Han","doi":"10.1016/j.molbiopara.2024.111636","DOIUrl":"10.1016/j.molbiopara.2024.111636","url":null,"abstract":"<div><p><em>Opisthorchis felineus</em>, <em>Opisthorchis viverrini</em>, and <em>Clonorchis sinensis</em> (family Opisthorchiidae) are parasitic flatworms that pose serious threats to humans in certain countries and cause opisthorchiasis/clonorchiasis. Opisthorchiid flukes parasitize the biliary tract of the host, causing cholangitis, cholecystitis, cholelithiasis and cholangiocarcinoma. In this review, we primarily focus on recent microRNAs (miRNAs) studies of opisthorchiid flukes and their definitive hosts. Many miRNAs are conserved and expressed in a developmentally stage specific manner in the three opisthorchiid flukes, which play important roles in the growth and development of Opisthorchiidae spp., as well as host-pathogen interactions. Some miRNAs might be potential biomarkers related to carcinogenesis of cholangiocarcinoma. Therefore, this review provides the basis for further investigating the roles of miRNAs in opisthorchiid flukes and their definitive hosts, as well as promoting the development of novel approaches to prevent and treat opisthorchiasis/clonorchiasis.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematological changes due to malaria – An update","authors":"Rana Hussein Naser ,&nbsp;Toktam Rajaii ,&nbsp;Bibi Razieh Hosseini Farash ,&nbsp;Seyyed javad Seyyedtabaei ,&nbsp;Vahid Hajali ,&nbsp;Fatemeh Sadabadi ,&nbsp;Ehsan Saburi","doi":"10.1016/j.molbiopara.2024.111635","DOIUrl":"10.1016/j.molbiopara.2024.111635","url":null,"abstract":"<div><p>Malaria, a parasitic infection caused by the genus <em>Plasmodium</em>, results to over 20 million reported cases annually worldwide. Most individuals exhibit various symptoms, and blood analysis plays a crucial role in determining the appropriate treatment approach. This study discusses various hematologic complications associated with different <em>Plasmodium</em> species. A review of scientific databases including PubMed, Science Direct, Web of Science, Scopus, EMBASE, Magiran, SID, IranMedex was conducted using standard keywords such as <em>Plasmodium</em>, malaria, anemia and blood disorders (hematologic disorder) between 2000 and 2024. The review focused on articles pertaining to clinical trials, prospective cohort, retrospective, cross-sectional and case-control studies. Articles evaluating the effects of malaria on blood cells and indices, with target groups including human and animals, were included. Articles not written in English or Farsi were excluded. Our review revealed that, apart from iron deficiency anemia and vascular dysfunction contributed in part by adhesion of infected RBC to endothelium, decreases in hematocrit and hemoglobin levels, as part of pancytopenia and thrombocytopenia, are characteristic of <em>Plasmodium</em> infection. Additionally, the occurrence of inflammation due to the release of inflammatory cytokines and complement activation can complicate the clinical features of malaria in individuals with hematologic conditions.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of the effect of bacterial stimulation on the global epigenetic landscape and transcription of immune genes in primarily zoophilic members of the Anopheles gambiae complex (Diptera: Culicidae)","authors":"Nashrin F. Patel ,&nbsp;Blaženka D. Letinić ,&nbsp;Leanne Lobb ,&nbsp;Jacek Zawada ,&nbsp;Dumsani M. Dlamini ,&nbsp;Nondumiso Mabaso ,&nbsp;Givemore Munhenga ,&nbsp;Shüné V. Oliver","doi":"10.1016/j.molbiopara.2024.111631","DOIUrl":"10.1016/j.molbiopara.2024.111631","url":null,"abstract":"<div><p>Members of the <em>Anopheles gambiae</em> complex vary in their vector competence, and this is often attributed to behavioural differences. Similarly, there are differences in transmission capabilities of the zoophilic members of this complex despite exhibiting similar behaviours. Therefore, behavioural differences alone cannot fully explain vector competence variation within members of the <em>An. gambiae</em> complex. The immune system of mosquitoes plays a key role in determining susceptibility to parasite infection and consequently transmission capacity. This study aimed to examine variations in the immune response of <em>An. arabiensis</em>, <em>An. merus</em> and <em>An. quadriannulatus</em>, a major, minor, and non-vector respectively. The global epigenetic landscape was characterised and the expression of <em>Defensin-1</em> and <em>Gambicin</em> was assessed in response to Gram-positive (<em>Streptococcus pyogenes</em>) and Gram-negative (<em>Escherichia coli</em>) bacterial infections. The effect of insecticide resistance in <em>An. arabiensis</em> on these aspects was also assessed. The immune system was stimulated by a blood-borne bacterial supplementation. The 5mC, 5hmC, m6A methylation levels and Histone Acetyl Transferase activity were assessed with commercial ELISA kits. The transcript levels of <em>Defensin-1</em> and <em>Gambicin</em> were assessed by quantitative Real-Time Polymerase Chain Reaction. Species-specific differences in 5mC and m6A methylation existed both constitutively as well as post immune stimulation. The epigenetic patterns observed in the laboratory strains were largely conserved in F1 offspring of wild-caught adults. The methylation patterns in the major vector typically differed from that of the minor/non-vectors. The differences between insecticide susceptible and resistant <em>An. arabiensis</em> were more reflected in the expression of <em>Defensin-1</em> and <em>Gambicin</em>. The expression of these peptides differed in the strains only after bacterial stimulation. <em>Anopheles merus</em> and <em>An. quadriannulatus</em> expressed significantly higher levels of antimicrobial peptides, both constitutively and after immune stimulation. These findings suggest molecular variations in the immune response of members of the <em>An</em>. <em>gambiae</em> complex.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166685124000240/pdfft?md5=319161ea823e45001410d6e3ca30ac04&pid=1-s2.0-S0166685124000240-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spirocerca lupi draft genome, vaccine and anthelmintic targets","authors":"Wiekolize Rothmann-Meyer ,&nbsp;Kershney Naidoo ,&nbsp;Pamela J. de Waal","doi":"10.1016/j.molbiopara.2024.111632","DOIUrl":"10.1016/j.molbiopara.2024.111632","url":null,"abstract":"<div><p><em>Spirocerca lupi</em> is a parasitic nematode affecting predominantly domestic dogs. It causes spirocercosis, a disease that is often fatal. The assembled draft genome of <em>S. lupi</em> consists of 13,627 predicted protein-coding genes and is approximately 150 Mb in length. Several known anthelmintic gene targets such as for β-Tubulin, glutamate, and GABA receptors as well as known vaccine gene targets such as cysteine protease inhibitor and cytokines were identified in <em>S. lupi</em> by comparing orthologs of <em>C. elegans</em> anthelmintic gene targets as well as orthologs to known vaccine candidates. New anthelmintic targets were predicted through an inclusion-exclusion strategy and new vaccine targets were predicted through an immunoinformatics approach. New anthelminthic targets include DNA-directed RNA polymerases, chitin synthase, polymerases, and other enzymes. New vaccine targets include cuticle collagens. These gene targets provide a starting platform for new drug identification and vaccine design.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166685124000252/pdfft?md5=30536aa8d35ccf82718a7e1b8f5f1cd6&pid=1-s2.0-S0166685124000252-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141247496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AlbuMAX supplemented media induces the formation of transmission-competent P. falciparum gametocytes","authors":"Wouter Graumans ,&nbsp;Alex van der Starre ,&nbsp;Rianne Stoter ,&nbsp;Geert-Jan van Gemert ,&nbsp;Chiara Andolina ,&nbsp;Jordache Ramjith ,&nbsp;Taco Kooij ,&nbsp;Teun Bousema ,&nbsp;Nicholas Proellochs","doi":"10.1016/j.molbiopara.2024.111634","DOIUrl":"10.1016/j.molbiopara.2024.111634","url":null,"abstract":"<div><p>Asexual blood stage culture of <em>Plasmodium falciparum</em> is routinely performed but reproducibly inducing commitment to and maturation of viable gametocytes remains difficult. Culture media can be supplemented with human serum substitutes to induce commitment but these generally only allow for long-term culture of asexual parasites and not transmission-competent gametocytes due to their different lipid composition. Recent insights demonstrated the important roles lipids play in sexual commitment; elaborating on this we exposed ring stage parasites (20–24 hours hpi) for one day to AlbuMAX supplemented media to trigger induction to gametocytogenesis. We observed a significant increase in gametocytes after AlbuMAX induction compared to serum. We also tested the transmission potential of AlbuMAX inducted gametocytes and found a significant higher oocyst intensity compared to serum. We conclude that AlbuMAX supplemented media induces commitment, allows a more stable and predictable production of transmittable gametocytes than serum alone.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0166685124000276/pdfft?md5=bcb32bafd94f80edeeb2f5ed2394903c&pid=1-s2.0-S0166685124000276-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic approaches for protein kinase substrate identification in Apicomplexa","authors":"Gabriel Cabral,&nbsp;William J. Moss,&nbsp;Kevin M. Brown","doi":"10.1016/j.molbiopara.2024.111633","DOIUrl":"10.1016/j.molbiopara.2024.111633","url":null,"abstract":"<div><p>Apicomplexa is a phylum of protist parasites, notable for causing life-threatening diseases including malaria, toxoplasmosis, cryptosporidiosis, and babesiosis. Apicomplexan pathogenesis is generally a function of lytic replication, dissemination, persistence, host cell modification, and immune subversion. Decades of research have revealed essential roles for apicomplexan protein kinases in establishing infections and promoting pathogenesis. Protein kinases modify their substrates by phosphorylating serine, threonine, tyrosine, or other residues, resulting in rapid functional changes in the target protein. Post-translational modification by phosphorylation can activate or inhibit a substrate, alter its localization, or promote interactions with other proteins or ligands. Deciphering direct kinase substrates is crucial to understand mechanisms of kinase signaling, yet can be challenging due to the transient nature of kinase phosphorylation and potential for downstream indirect phosphorylation events. However, with recent advances in proteomic approaches, our understanding of kinase function in Apicomplexa has improved dramatically. Here, we discuss methods that have been used to identify kinase substrates in apicomplexan parasites, classifying them into three main categories: i) kinase interactome, ii) indirect phosphoproteomics and iii) direct labeling. We briefly discuss each approach, including their advantages and limitations, and highlight representative examples from the Apicomplexa literature. Finally, we conclude each main category by introducing prospective approaches from other fields that would benefit kinase substrate identification in Apicomplexa.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of Toxoplasma gondii SRS29C nucleic acid vaccine and comparative immunoprotective study of an SRS29C and SAG1 combination","authors":"An Yan,&nbsp;Jing Tian,&nbsp;Jianjun Ye,&nbsp;Chuanliang Gao,&nbsp;Liying Ye,&nbsp;Dongchao Zhang,&nbsp;Qiqi Song","doi":"10.1016/j.molbiopara.2024.111630","DOIUrl":"10.1016/j.molbiopara.2024.111630","url":null,"abstract":"<div><p><em>Toxoplasma gondii</em> is an intracellular protozoan parasite that infects all nucleated cells except the red blood cells. Currently, nucleic acid vaccines are being widely investigated in <em>Toxoplasma gondii</em> control, and several nucleic acid vaccine candidate antigens have shown good protection in various studies. The aim of this study was to construct a nucleic acid vaccine with <em>Toxoplasma gondii</em> SRS29C as the target gene. We explored the nucleic acid vaccine with <em>Toxoplasma</em> surface protein SRS29C and the combined gene of SRS29C and SAG1 and evaluated its immunoprotective effect against <em>Toxoplasma gondii.</em> To amplify the gene fragment and clone it to the expression vector, the recombinant plasmid pEGFP-SRS29C was constructed by PCR. Eukaryotic cells were transfected with the plasmid, and the expression of the target protein was assessed using the Western blot method. The level of serum IgG was determined via ELISA, and the splenic lymphocyte proliferation ability was detected using the CCK-8 method. The percentages of CD4⁺ and CD8⁺ T cells were measured by flow cytometry. Mice were immunised three times with single-gene nucleic acid vaccine and combination vaccine. Splenic lymphocytokine expression was determined using ELISA kits. The mice's survival time was monitored and recorded during an in vivo insect assault experiment, and the vaccine's protective power was assessed. The outcomes showed that PCR-amplification of an SRS29C gene fragment was successful. The 4,733-bp vector fragment and the 1,119-bp target segment were both recognised by double digestion. Additionally, after transfection of the recombinant plasmid pEGFP-SRS29C, Western blot examination of the extracted protein revealed the presence of a target protein strip at 66 kDa. The test results demonstrated that the IgG content in the serum of the pEGFP-SRS29C group and the co-immunization group was significantly higher than that of the PBS group and the empty vector group. The IgG potency induced by the co-immunization group was higher than that of the pEGFP-SRS29C group and the pEGFP-SAG1 group, the number of splenic lymphocyte proliferation number was higher than that of the PBS group and the empty vector group. The CD4⁺/CD8⁺ T ratio was higher than that of the PBS group and the empty vector group. The expression of IFN-γ and TNF-α in the splenocytes of the pEGFP-SRS29C group and the combined immunisation group was significantly higher following antigen stimulation. In the worm attack experiments, mice in the PBS and empty vector groups perished within 9 days of the worm attack, whereas mice in the pEGFP-SRS29C group survived for 18 days, mice in the pEGFP-SAG1 group survived for 21 days, and mice in the co-immunization group survived for 24 days. This demonstrates that the constructed <em>Toxoplasma gondii</em> nucleic acid vaccine pEGFP-SRS29C and the combined gene vaccine can induce mice to","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141136626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Leishmania activity and molecular docking of unusual flavonoids-rich fraction from Arrabidaea brachypoda (Bignoniaceae)","authors":"Monica A. das Neves ,&nbsp;Jessyane R. do Nascimento ,&nbsp;Vera Lucia Maciel-Silva ,&nbsp;Alberto M. dos Santos ,&nbsp;Jaldyr de Jesus G.V. Junior ,&nbsp;Ana Jessica S. Coelho ,&nbsp;Mayara Ingrid S. Lima ,&nbsp;Silma Regina F. Pereira ,&nbsp;Cláudia Q. da Rocha","doi":"10.1016/j.molbiopara.2024.111629","DOIUrl":"10.1016/j.molbiopara.2024.111629","url":null,"abstract":"<div><p>Leishmaniases comprise a group of infectious parasitic diseases caused by various species of <em>Leishmania</em> and are considered a significant public health problem worldwide. Only a few medications, including miltefosine, amphotericin B, and meglumine antimonate, are used in current therapy. These medications are associated with severe side effects, low efficacy, high cost, and the need for hospital support. Additionally, there have been occurrences of drug resistance. Additionally, only a limited number of drugs, such as meglumine antimonate, amphotericin B, and miltefosine, are available, all of which are associated with severe side effects. In this context, the need for new effective drugs with fewer adverse effects is evident. Therefore, this study investigated the anti-<em>Leishmania</em> activity of a dichloromethane fraction (DCMF) extracted from <em>Arrabidaea brachypoda</em> roots. This fraction inhibited the viability of <em>L. infantum</em>, <em>L. braziliensis</em>, and <em>L. Mexicana</em> promastigotes, with IC₅₀ values of 10.13, 11.44, and 11.16 µg/mL, respectively, and against <em>L. infantum</em> amastigotes (IC₅₀ = 4.81 µg/mL). Moreover, the DCMF exhibited moderate cytotoxicity (CC₅₀ = 25.15) towards RAW264.7 macrophages, with a selectivity index (SI) of 5.2. Notably, the DCMF caused damage to the macrophage genome only at 40 µg/mL, which is greater than the IC₅₀ found for all <em>Leishmania</em> species. The results suggest that DCMF demonstrates similar antileishmanial effectiveness to isolated brachydin B, without causing genotoxic effects on mammalian cells. This finding is crucial because the isolation of the compounds relies on several steps and is very costly while obtaining the DCMF fraction is a simple and cost-effective process. Furthermore, In addition, the potential mechanisms of action of brachydins were also investigated. The computational analysis indicates that brachydin compounds bind to the Triosephosphate isomerase (TIM) enzyme via two main mechanisms: destabilizing the interface between the homodimers and interacting with catalytic residues situated at the site of binding. Based on all the results, DCMF exhibits promise as a therapeutic agent for leishmaniasis due to its significantly reduced toxicity in comparison to the adverse effects associated with current reference treatments.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}