{"title":"Stabilization and characterization of Phyllanthus acidus L. leaf synthesized metal nanoparticles and their comparative efficacy as larvicides against three vector mosquitoes","authors":"Arpita Gope, Anjali Rawani","doi":"10.1016/j.exppara.2025.108968","DOIUrl":"10.1016/j.exppara.2025.108968","url":null,"abstract":"<div><div>The recurring global outbreaks of mosquito-borne diseases and the lack of vaccines, and preventive therapeutic approaches to combat diseases coupled with insecticide resistance, eventually emphasize the necessity of developing biological system-focused mosquito control strategies. In the present study, aqueous leaf extract from the <em>Phyllanthus acidus</em> L. plant was used to synthesize the metal nanoparticles (MNPs) such as silver, copper oxide, iron oxide, and zinc oxide, characterization has been carried out and their efficacies were also tested against the early 3rd instar larvae of the major mosquito vectors. According to analytical characterization, the silver (Ag), copper (CuO), iron (FeO), and zinc (ZnO) NPs had face-centered cubic crystallites with average sizes of 50, 52.33, 40.56, and 79.45nm, respectively. The agglomerated and clustered surface shape of MNPs was confirmed by FE-SEM analysis, and EDX tests were used to determine the fundamental composition of each particle. When exposed to 1, 5, 10, 15, and 20 ppm of metal nanoparticles, the larvicidal activity of silver nanoparticles was found to be superior to that of other nanoparticles demonstrating efficacy in the following order: silver > iron > copper > zinc against the larvae of filarial vector <em>Culex quinquefasciatus,</em> Japanese encephalitis vector <em>Culex vishnui</em> and dengue vector <em>Aedes albopictus</em>. After 72 h of exposure, the AgNPs had very little detrimental impact on the non-targeted organisms (<em>Chironomus</em> sp. larvae), causing 3.33 % of deaths. The exposure of MNPs to control larval body homogenates resulted in a considerable decrease in the key esterase enzymes, namely acetylcholinesterase, α-and β-carboxyl esterase, and GST enzymes. According to the present results, MNPs made from <em>P. acidus leaf</em> extracts have a strong enough negative effect to reduce the prevalence of vector mosquitoes.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"275 ","pages":"Article 108968"},"PeriodicalIF":1.4,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144368727","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":"Evaluation of β-caryophyllene(1–3) as a potential anti-tick molecule for controlling tick infestations on animals","authors":"Gajanan M. Chigure , Anil Kumar Sharma , K.G. Ajithkumar , Ashutosh Fular , Amol B. Tayade , Rajesh Kumar , Nitin D. Jadhav , Sachin Kumar , Suman Gupta , Gaurav Nagar , Reghu Ravindran , Satyanshu Kumar , Sanis Julliet , Muthu Sankar , Srikanta Ghosh","doi":"10.1016/j.exppara.2025.108969","DOIUrl":"10.1016/j.exppara.2025.108969","url":null,"abstract":"<div><div><em>Ageratum conyzoides</em> (Family: Asteraceae), a common herbaceous weed has a long history of use in traditional medicine. <em>Rhipicephalus microplus,</em> the cattle tick is distributed globally and causing significant economic losses to the animal husbandry sectors. Due to repeated applications of chemical acaricides to control infestation on animals, the tick species developed resistance to most of the acaricides. In the present study, to manage the problem of resistant ticks, the potentiality of <em>β-caryophyllene (1–3)</em> is explored for its anti-tick efficacy against three important tick species. The LC<sub>95</sub> value of <em>β-caryophyllene (1–3)</em> against reference susceptible IVRI-I strain of <em>R. microplus</em> was 0.0284 % (95 % CI = 266.5–299.4) while against multi-acaricide resistant field isolates it was 0.0507 % (95 % CI = 491.4–523.0). The compound was 95 % efficacious against <em>Hyalomma anatolicum</em> and <em>R</em>. <em>annulatus</em> ticks. The anti-tick efficacy of the compound after oral administration at the dose rate of 7.5 mg per kg body weight was tested under challenged infestation conditions and more than 80 % efficacy was noted. In a separate experiment, a 73.3–97.7 % (mean efficacy = 77.6 %) efficacy of <em>β-caryophyllene (1–3)</em> was noted for three months which was comparable and not significantly lower than the efficacy (95.8 %) observed in the amitraz treatment group of animals but significantly higher as compared to the control group of animals. The present study was focused on the identification of new plant derived anti-tick molecule having the acaricidal capability for the management of resistant tick infestations on animals.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"274 ","pages":"Article 108969"},"PeriodicalIF":1.4,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340056","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":"Role of IFN-γ and IL-10 cytokines and associated genes on Haemonchus contortus infection in resistant and susceptible Garole sheep","authors":"Supradip Das , Ananta Hembram , Ruma Jas , Shamik Polley , Joydip Mukherjee , Shyam Sundar Kesh , Soumitra Pandit , Surajit Baidya , Abhijit Nandi , Uttam Sarkar , Subhas Chandra Mandal","doi":"10.1016/j.exppara.2025.108970","DOIUrl":"10.1016/j.exppara.2025.108970","url":null,"abstract":"<div><div>Role of IFN-γ and IL-10 cytokines and associated genes (<em>IFN-γ</em> and <em>IL-10</em>) on <em>Haemonchus contortus</em> resistance was studied in experimentally infected resistant and susceptible Garole sheep. Nine resistant and nine susceptible Garole sheep were selected based on faecal egg counts (FEC) and divided into 3 groups; uninfected control (n = 6), infected resistant (n = 6) and infected susceptible (n = 6). Sheep of infected groups were orally challenged with 500 <em>H. contortus</em> infective larvae per kg body weight of experimental sheep. Faecal egg counts were measured from 18 days post infection (DPI) at 3 days intervals for nine occasions, and plasma cytokines (IFN-γ and IL-10) concentration and expressions of cytokine genes (<em>IFN-γ</em> and <em>IL-10</em>) expressions were measured from 0 DPI to 40 DPI at 10 days intervals. Resistant sheep had significantly (P < 0.001) lower FEC from 27 DPI onwards compared to susceptible sheep and subsequently no eggs were found in resistant sheep from 33 DPI onwards. In resistant sheep, significantly higher concentration of IFN-γ cytokine and expression of <em>IFN-γ</em> gene were observed at early stage (10–20 DPI), and IL-10 cytokine production and <em>IL-10</em> gene expression upregulated at later stage of infection (20–30 DPI) after which there was significant reduction of egg output in faeces of resistant group of sheep. Hence in Garole sheep both the IFN-γ and IL-10 cytokines and their associated genes might be linked with <em>H. contortus</em> resistance with <em>IL-10</em> cytokine gene playing comparatively more active role in development of resistance to <em>H. contortus</em>.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"274 ","pages":"Article 108970"},"PeriodicalIF":1.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322915","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}
Thayná Couto de Barros , Roberto do Val Vilela , Rosana Gentile , Karina Varella , Juberlan Silva Garcia , Thiago dos Santos Cardoso , Beatriz Elise de Andrade-Silva , Aline dos Santos Moreira , Beatriz de Lima Alessio Müller , Alexandre Araujo Cunha dos Santos , Daiani Cotrim de Paiva Campbell , Arnaldo Maldonado Júnior
{"title":"Praziquantel effect on genetic diversity of wild rodent-derived Schistosoma mansoni in experimentally infected mice","authors":"Thayná Couto de Barros , Roberto do Val Vilela , Rosana Gentile , Karina Varella , Juberlan Silva Garcia , Thiago dos Santos Cardoso , Beatriz Elise de Andrade-Silva , Aline dos Santos Moreira , Beatriz de Lima Alessio Müller , Alexandre Araujo Cunha dos Santos , Daiani Cotrim de Paiva Campbell , Arnaldo Maldonado Júnior","doi":"10.1016/j.exppara.2025.108963","DOIUrl":"10.1016/j.exppara.2025.108963","url":null,"abstract":"<div><div>Praziquantel (PZQ) is currently the only drug recommended by the World Health Organization (WHO) for treating schistosomiasis, raising concerns about potential resistance. Frequent use of PZQ may reduce the genetic diversity of <em>Schistosoma mansoni</em>, affecting its adaptability and survival. The objective of this study was to test the impact of Praziquantel treatment and population bottlenecks on the genetic diversity of <em>S. mansoni</em> by experimental infection using a wild strain isolated from naturally infected rodents. Experimental infections were conducted in outbred mice, which were infected with 120 cercariae, and treated with two different doses of PZQ (3 × 150 mg/kg and 3 × 300 mg/kg) at 50, 51, and 52 days post-exposure, and necropsied 15 days later. Microsatellites and MT-CO1 were used as molecular markers. An 85.5 % reduction in parasite load (p = 0.04) was observed after 300 mg/kg PZQ treatment, with greater efficacy in male worms. MT-CO1 analysis identified two haplotypes differing by one polymorphic site, with one haplotype representing 84.2 % of the population. Low genetic differentiation was observed for MT-CO1. All seven microsatellite loci studied exhibited polymorphisms, with 3–7 alleles per locus. Praziquantel treatment caused population bottleneck, reduced genetic variability in both dosage groups: IT150 (R<sub>ST</sub> = 0.14043, p = 0.000) and IT300 (R<sub>ST</sub> = 0.13610, p = 0.005), and eliminated alleles with low initial frequencies. We concluded that microsatellite markers showed genetic differentiation with elimination of rare alleles, confirming the genetic bottleneck effect due to treatment with PZQ.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"274 ","pages":"Article 108963"},"PeriodicalIF":1.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198633","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}
Rodolfo Gamaliel Avila-Bonilla , Jorge A. Velázquez Guzmán , Esther Ramírez-Moreno , Laurence A. Marchat
{"title":"A network of RNA-binding and metabolic proteins evidenced in the Entamoeba histolytica nuclear proteome","authors":"Rodolfo Gamaliel Avila-Bonilla , Jorge A. Velázquez Guzmán , Esther Ramírez-Moreno , Laurence A. Marchat","doi":"10.1016/j.exppara.2025.108965","DOIUrl":"10.1016/j.exppara.2025.108965","url":null,"abstract":"<div><div>Amoebiasis caused by the protozoan parasite <em>Entamoeba histolytica</em> is a serious leading cause of parasite-related death worldwide and there is a need for developing new safe and efficient control methods. The nuclear polyadenylation factor EhCFIm25 has been recently reported as a biochemical target in <em>E. histolytica,</em> being necessary for proliferation and parasite virulence. Interestingly, the prediction and experimental characterization of EhCFIm25 interactome revealed close relationships between nuclear proteins involved in gene expression regulation and typically cytoplasmic enzymes of redox and energy metabolism. Here, the description of the nuclear proteome of <em>E. histolytica</em> obtained by mass spectrometry analysis confirmed the presence of metabolic proteins in the nuclear compartment, which could have moonlight functions. Data are available via ProteomeXchange with identifier PXD056950. The predicted network of RNA-binding and metabolic proteins also evidenced the relevance of five metabolic enzymes in the coordination between energy and RNA metabolism, opening new perspectives for amoebiasis control.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"274 ","pages":"Article 108965"},"PeriodicalIF":1.4,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184988","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}
Victória Hannah Araújo de Almeida Passos , Paulline Paiva Mendes de Souza Leal , Pastora Pereira Lima Neta , Evellyn Caroline Silva Melo , Vinicius Santos Silva , Glaucia Lais Nunes Lopes , Matheus Oliveira do Nascimento , Elvilene de Sousa Coelho , Sérgio Paulo Lima Guerra , Ana Karina Marques Fortes Lustosa , Vitória de Cássia Coelho Rodrigues , André Luis Menezes Carvalho , Fernando Aécio de Amorim Carvalho , Michel Mualem de Moraes Alves
{"title":"Topical formulation of Oseltamivir promotes clinical improvement and reduction of parasite load in BALB/c mice infected with Leishmania major","authors":"Victória Hannah Araújo de Almeida Passos , Paulline Paiva Mendes de Souza Leal , Pastora Pereira Lima Neta , Evellyn Caroline Silva Melo , Vinicius Santos Silva , Glaucia Lais Nunes Lopes , Matheus Oliveira do Nascimento , Elvilene de Sousa Coelho , Sérgio Paulo Lima Guerra , Ana Karina Marques Fortes Lustosa , Vitória de Cássia Coelho Rodrigues , André Luis Menezes Carvalho , Fernando Aécio de Amorim Carvalho , Michel Mualem de Moraes Alves","doi":"10.1016/j.exppara.2025.108966","DOIUrl":"10.1016/j.exppara.2025.108966","url":null,"abstract":"<div><div>Leishmaniasis is a parasitic disease caused by protozoa of the genus <em>Leishmania</em>, the conventional treatments are expensives, high adverse reactions and long-term parenteral administration This study aimed to evaluate the therapeutic potential of the antiviral Oseltamivir (Osv) in microemulsion in the topical treatment of cutaneous leishmaniasis in BALB/c mice infected with <em>Leishmania major</em>. After infection, the mice were divided into five groups (Control, Amphotericin B 3 %, Osv 0.5 %, Osv 1 % and Osv 1 %+Amphotericin B 1.5 %) and treated for 21 days. Clinical parameters, such as body weight and lesion size, in addition to parasite load, hematological, biochemical and histopathological analyses were evaluated. A significant reduction in the parasite load was observed in the groups treated with Oseltamivir and Amphotericin B (70 %–76.5 %), when compared to the control group (95 %). Clinical evaluation showed fewer lesions in the treatment groups compared to the control group. Although Amphotericin B alone caused liver and kidney toxicity, treatment with Oseltamivir, alone or in combination with Amphotericin B, did not show any toxicity. In histopathological examination, the groups treated with Oseltamivir showed lower degrees of histopathological alterations. Thus, Oseltamivir, as monotherapy or in combination with Amphotericin B, proved to be effective and safe, representing a promising alternative in the treatment of cutaneous leishmaniasis.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"274 ","pages":"Article 108966"},"PeriodicalIF":1.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180562","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":"Efficacy of essential oil from Maranta arundinacea L. against immature stages of dengue, filariasis, and malaria vectors and four mosquito predators","authors":"Pathalam Ganesan , Jeyaraj Selvakumaran , Natarajan Ganapathy Muthukumar , Mariappan Muthukanagavel , Subramanian Mutheeswaran , Savarimuthu Ignacimuthu , Rajakrishnan Rajagopal , Ahmed Alfarhan , Arokiyaraj Selvaraj","doi":"10.1016/j.exppara.2025.108964","DOIUrl":"10.1016/j.exppara.2025.108964","url":null,"abstract":"<div><div>Mosquitoes are significant vectors of infectious diseases, causing thousands of fatalities worldwide each year. This present study was to check the toxicity of essential oil (EO) from <em>Maranta arundinacea</em> L. against three mosquito species: <em>Anopheles stephensi, Culex quinquefasciatus</em> and <em>Aedes aegypti</em>. The immature stages were exposed to five different concentrations such as 3.125, 6.25, 12.5, 25 and 50 ppm; these were used to check the insecticidal activity according to WHO standard protocol with slight modification. The EO presented 100 % ovicidal toxicity against the eggs of treated three mosquitoes at 24 h. Strong mosquitocidal effects were observed, with LC<sub>50</sub> values of 5.0, 4.9 and 6.2 ppm for the larvae (3rd Instar) of <em>Anopheles, Culex</em> and <em>Aedes</em> species, respectively, at 24 h. However, no significant pupicidal toxicity was observed in any of the mosquito. Three main compounds were identified in the EO that might have contributed to its mosquitocidal properties. Toxicity assessments indicated that the EO from <em>M. arundinacea</em> did not adversely affect the tested natural predators such as <em>P. reticulata,</em> Dragon fly nymph, <em>D. indicus</em> and <em>G. affinis</em>. The EO was then formulated for field application, which confirmed its promising mosquitocidal activity (20–28 ppm), without any toxicity to tested natural predators. This study highlights the potential of EO from <em>M. arundinacea</em> in mosquito management, suggesting that it can serve as a possible substitute to synthetic chemicals, offering effective mosquito control with minimal environmental impact.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"274 ","pages":"Article 108964"},"PeriodicalIF":1.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131428","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":"Cystic echinococcosis susceptibility is increased by polymorphisms in the transporter associated with antigen processing 1 and 2 genes","authors":"Susan Jabbaripour , Siamak Sandoghchian Shotorbani , Adel Spotin , Ehsan Ahmadpour , Navid Shomali , Mahmoud Mahami-Oskouei","doi":"10.1016/j.exppara.2025.108943","DOIUrl":"10.1016/j.exppara.2025.108943","url":null,"abstract":"<div><div>Susceptibility or resistance to various diseases, especially parasitic infections, largely depends on immune system function and genetics. Single nucleotide polymorphisms on the TAP1-637 and TAP2-379 genes may play a role in hydatidosis by affecting the immune system.</div><div>This study was conducted as a case-control study. After confirmation by serological ELISA method, blood samples were collected from 76 people with hydatid cyst and also from 76 healthy people. DNA was extracted from the samples and the ARMS-PCR technique was used to identify mutations. To evaluate the accuracy and ensure the PCR results, some samples were also sequenced in two groups with different genotypes.</div><div>Compared to the control group, the case group (infected group) had a higher frequency of the heterozygous Asp/Gly codon 637 of the TAP1 gene. In addition, the frequency of the Gly phenotype and allele was higher in the infected group (<em>P</em> < 0.05). Furthermore, the infected group had a higher frequency of the heterozygous Val/Ile codon 379 of the TAP2 gene. The frequency of the Ile phenotype and allele was also higher in the infected group than in the control group (<em>P</em> < 0. 05).</div><div>The results of this study showed that the Gly allele and Asp/Gly genotype in codon 637 of the TAP1 gene, as well as the Ile allele and Val/Ile genotype in codon 379 of the TAP2 gene are considered genetic risk factors for cystic echinococcosis.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"272 ","pages":"Article 108943"},"PeriodicalIF":1.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917321","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":"Identification of therapeutics against PfPK6 protein of Plasmodium falciparum: Structure and Deep Learning approach","authors":"Sibasish Sarangi, Rajani Kanta Mahapatra","doi":"10.1016/j.exppara.2025.108947","DOIUrl":"10.1016/j.exppara.2025.108947","url":null,"abstract":"<div><div>The <em>Plasmodium falciparum</em> Protein Kinase 6 (PfPK6) is a serine/threonine protein kinase categorized under the CMGC group, displaying both cyclin-dependent kinases (CDKs) and mitogen-activated protein kinases (MAPKs) activity. Previous research has indicated that PfPK6 is expressed during the trophozoite and schizont stages of the <em>Plasmodium falciparum</em> asexual blood stage. Unlike typical cyclin-dependent kinases, PfPK6 demonstrates kinase activity independent of cyclin, making it a promising target for drug identification. In this study, we utilized a computational approach to identify a novel PfPK6 inhibitor through virtual screening of small inhibitor compounds from diverse datasets, employing a structure-based approach and a Deep Learning (DL) model. The most promising inhibitor molecule, TCMDC-132409 from the Tres Cantos Antimalarial Set, exhibited a binding affinity of −13.553 kcal/mol against PfPK6. Additionally, a 200ns molecular dynamics simulation study confirmed the stability of the binding mode, indicating the potential of TCMDC-132409 as an antiplasmodial inhibitor for further investigation.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"273 ","pages":"Article 108947"},"PeriodicalIF":1.4,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894559","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":"Molecular docking, toxicity study and in vitro antimalarial evaluation of pyrazole substituted 1,3,5-triazine derivatives","authors":"Bonita Chetia , Anshul Shakya , Surajit Kumar Ghosh , Sathishkumar Vinayagam , Saurav Jyoti Patgiri , Ipsita Pal Bhowmick , Udaya Pratap Singh , Hans Raj Bhat","doi":"10.1016/j.exppara.2025.108945","DOIUrl":"10.1016/j.exppara.2025.108945","url":null,"abstract":"<div><div>The development of resistance to antimalarial drugs such as chloroquine, amodiaquine, artemisinin, and antifolates is a major health concern, prompting more research into new antimalarial therapies. In the present study, we intend to develop pyrazole substituted 1,3,5-triazine derivatives <strong>7</strong>(<strong>a</strong>-<strong>j</strong>) as antimalarial agents. These compounds were synthesized using conventional methods and analyzed using various spectroscopic techniques. The docking results showed that compounds <strong>7j</strong> and <strong>7i</strong> exhibited an excellent binding interactions with PRO A:113, ILE A:164, SER A:111, PHE A:58, LEU A:46, LEU A:119, VAL A:45, ILE A:112 (−204.97to −118.41 kcal/mol) and TYR A:170, CYS A:15, PRO A:113, ILE A:112, ALA A:16, PHE A:58, MET A:55, SER A:111 (−216.24to −152.06 kcal/mol) against wild (1J3I) and quadruple mutant (1J3K) type of <em>Pf</em>-DHFR-TS. Compounds <strong>7j</strong> and <strong>7i</strong> exhibited considerable antimalarial efficacy against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains of <em>P. falciparum</em>, with IC<sub>50</sub> values ranging from 23.78 to 83.36 μM and 30.89–64.24 μM, respectively. These pyrazole-substituted 1,3,5-triazine derivatives could be utilized to find a novel class of <em>Pf</em>-DHFR-TS inhibitors.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"273 ","pages":"Article 108945"},"PeriodicalIF":1.4,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881432","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}