{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:16:46Z","timestamp":1787894206229,"version":"build-2784847793"},"reference-count":64,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"E022 Program, National Institute of Pediatrics, Mexico City, Mexico"},{"name":"INP","award":["020\/2025"],"award-info":[{"award-number":["020\/2025"]}]},{"DOI":"10.13039\/501100009609","name":"Fondos Federales","doi-asserted-by":"publisher","award":["HIM\/2019\/036 SSA.1595"],"award-info":[{"award-number":["HIM\/2019\/036 SSA.1595"]}],"id":[{"id":"10.13039\/501100009609","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Secretar\u00eda de Ciencia, Humanidades, Tecnolog\u00eda e Innovaci\u00f3n (SECIHTI), Ciencia de Frontera 2023","doi-asserted-by":"publisher","award":["CF-2023-I-811"],"award-info":[{"award-number":["CF-2023-I-811"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CF-2023-I-811"],"award-info":[{"award-number":["CF-2023-I-811"]}],"id":[{"id":"https:\/\/ror.org\/059ex5q34","id-type":"ROR","asserted-by":"publisher"}]},{"name":"IPICyT\u2019s National Supercomputing Center"},{"name":"CNS","award":["TKII-E-0325-I-280325-64\/PR-64"],"award-info":[{"award-number":["TKII-E-0325-I-280325-64\/PR-64"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Giardiasis remains a significant global health issue, and its treatment is increasingly hampered by the emergence of drug resistance and cross-resistance between nitroimidazoles and nitazoxanide. In this study, we evaluated the in vitro antigiardial activity, cytotoxicity, and potential mechanisms of action of seven structural analogs (CLB 1\u20137) derived from a hybrid structure combining nitazoxanide and clofibric acid. Among them, compounds CLB-3 and CLB-5 emerged as the most potent candidates, demonstrating exceptional efficacy against a nitazoxanide-resistant (NTZr) strain of Giardia lamblia, with potencies up to 43 and 60 times higher than that of the reference drug, respectively. Furthermore, both compounds demonstrated high selectivity for the parasite, exhibiting low cytotoxicity in human Caco-2 cells. To investigate the mechanism of action, functional biochemical assays revealed that treatment with these derivatives significantly reduced the intracellular ATP levels and altered the ADP\/ATP ratio, indicating a direct impact on the parasite\u2019s energy metabolism. These functional findings correlate closely with RT-qPCR transcriptional analyses and in silico molecular dynamics simulations; collectively, the data suggest a multi-target mechanism of action that may involve the disruption of energy homeostasis and the possible inhibition of key enzymes in the glycolytic pathway (PFOR, G6PD::6PGL, PK, and PPDK). In summary, these results identify compounds CLB-3 and CLB-5 as highly promising chemotherapeutic candidates for combating refractory giardiasis.<\/jats:p>","DOI":"10.3390\/molecules31172980","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T09:05:46Z","timestamp":1787735146000},"page":"2980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["5-Nitrothiazol-Clofibric Acid Analogs as Potent Agents Against Nitazoxanide-Resistant Giardia lamblia: Modulation of Glycolytic Genes and Molecular Dynamics Studies"],"prefix":"10.3390","volume":"31","author":[{"given":"Beatriz","family":"Hern\u00e1ndez-Ochoa","sequence":"first","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n en Ciencias \u00d3micas y Epidemiolog\u00eda Microbiana, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5678-5618","authenticated-orcid":false,"given":"Blanca","family":"Colin-Lozano","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidad La Salle, Mexico City 06140, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5344-4762","authenticated-orcid":false,"given":"Gabriel","family":"Navarrete-V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia, Universidad Aut\u00f3noma del Estado de Morelos, Cuernavaca 62209, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2058-5707","authenticated-orcid":false,"given":"Sergio","family":"Enr\u00edquez-Flores","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomol\u00e9culas y Salud Infantil, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-8089","authenticated-orcid":false,"given":"Ignacio","family":"De la Mora-De la Mora","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomol\u00e9culas y Salud Infantil, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1451-8754","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"P\u00e9rez de la Cruz","sequence":"additional","affiliation":[{"name":"Neurobiochemistry and Behavior Laboratory, National Institute of Neurology and Neurosurgery \u201cManuel Velasco Su\u00e1rez\u201d, Mexico City 14269, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4611-4770","authenticated-orcid":false,"given":"Roberto","family":"Arreguin-Espinosa","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica de Biomacromol\u00e9culas, Instituto de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de M\u00e9xico, M\u00e9xico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4117-6689","authenticated-orcid":false,"given":"Rosa Ang\u00e9lica","family":"Castillo-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n en Ciencia Aplicada y Tecnolog\u00eda Avanzada (CICATA) Unidad Morelos, Instituto Polit\u00e9cnico Nacional, Xochitepec 62790, Morelos, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3617-8148","authenticated-orcid":false,"given":"Jos\u00e9 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Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1017\/S0950268818001073","article-title":"Risk factors for sporadic Giardia infection in the USA: A case-control study in Colorado and Minnesota","volume":"146","author":"Reses","year":"2018","journal-title":"Epidemiol. Infect."},{"key":"ref_3","first-page":"910","article-title":"Prevalence and Clinical Manifestations of Giardia intestinalis and Other Intestinal Parasites in Children and Adults in Algeria","volume":"104","author":"Belkessa","year":"2021","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_4","first-page":"3","article-title":"Giardia lamblia infection: Review of current diagnostic strategies","volume":"12","author":"Hooshyar","year":"2019","journal-title":"Gastroenterol. Hepatol. Bed Bench"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"6366","DOI":"10.3748\/wjg.v12.i39.6366","article-title":"Randomized clinical study of five days apostrophe therapy with mebendazole compared to quinacrine in the treatment of symptomatic giardiasis in children","volume":"12","author":"Canete","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1517\/14656566.8.12.1885","article-title":"Giardiasis: A pharmacotherapy review","volume":"8","author":"Escobedo","year":"2007","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1093\/jac\/46.5.819","article-title":"Metronidazole and albendazole susceptibility of 11 clinical isolates of Giardia duodenalis from France","volume":"46","author":"Zaharia","year":"2000","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/s40475-015-0051-1","article-title":"Drug Resistance in the Microaerophilic Parasite Giardia lamblia","volume":"2","author":"Leitsch","year":"2015","journal-title":"Curr. Trop. MedRep"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1093\/jac\/dkm205","article-title":"Characterization of Giardia lamblia WB C6 clones resistant to nitazoxanide and to metronidazole","volume":"60","author":"Sterk","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4643","DOI":"10.1128\/AAC.00384-11","article-title":"Impaired parasite attachment as fitness cost of metronidazole resistance in Giardia lamblia","volume":"55","author":"Millman","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"taab120","DOI":"10.1093\/jtm\/taab120","article-title":"Treatment strategies for nitroimidazole-refractory giardiasis: A systematic review","volume":"29","author":"Bourque","year":"2022","journal-title":"J. Travel Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.3201\/eid3106.250076","article-title":"Prevalence of Nitroimidazole-Refractory Giardiasis Acquired in Different World Regions, Sweden, 2008\u20132020","volume":"31","author":"Ydsten","year":"2025","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1128\/AAC.00618-10","article-title":"High-throughput Giardia lamblia viability assay using bioluminescent ATP content measurements","volume":"55","author":"Chen","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.mimet.2010.12.026","article-title":"An image-based assay for high throughput screening of Giardia lamblia","volume":"84","author":"Gut","year":"2011","journal-title":"J. Microbiol. Methods"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1093\/jac\/dkp363","article-title":"Stable expression of Escherichia coli beta-glucuronidase A (GusA) in Giardia lamblia: Application to high-throughput drug susceptibility testing","volume":"64","author":"Nillius","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3490","DOI":"10.1016\/j.bmcl.2017.05.071","article-title":"Synthesis, in vitro and in vivo giardicidal activity of nitrothiazole-NSAID chimeras displaying broad antiprotozoal spectrum","volume":"27","author":"Scior","year":"2017","journal-title":"Bioorg Med. Chem. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1016\/j.bmc.2015.02.059","article-title":"Synthesis of nitro(benzo)thiazole acetamides and in vitro antiprotozoal effect against amitochondriate parasites Giardia intestinalis and Trichomonas vaginalis","volume":"23","year":"2015","journal-title":"Bioorg Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"21","DOI":"10.2174\/1573409911666150414145937","article-title":"Antiprotozoal Nitazoxanide Derivatives: Synthesis, Bioassays and QSAR Study Combined with Docking for Mechanistic Insight","volume":"11","author":"Scior","year":"2015","journal-title":"Curr. Comput. Aided Drug Des."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1016\/j.bmc.2014.01.029","article-title":"2-acylamino-5-nitro-1,3-thiazoles: Preparation and in vitro bioevaluation against four neglected protozoan parasites","volume":"22","year":"2014","journal-title":"Bioorg Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Morales-Luna, L., Hern\u00e1ndez-Ochoa, B., Gonz\u00e1lez-Valdez, A., V\u00e1zquez-Bautista, M., Arreguin-Espinosa, R., P\u00e9rez de la Cruz, V., Enr\u00edquez-Flores, S., De la Mora De la Mora, I., Hern\u00e1ndez-Urz\u00faa, E., and Castillo-Rodr\u00edguez, R.A. (2025). Nitazoxanide Analogs: Synthesis, In Vitro Giardicidal Activity, and Effects on Giardia lamblia Metabolic Gene Expression. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26104504"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e02397-16","DOI":"10.1128\/AAC.02397-16","article-title":"Click Chemistry-Facilitated Structural Diversification of Nitrothiazoles, Nitrofurans, and Nitropyrroles Enhances Antimicrobial Activity against Giardia lamblia","volume":"61","author":"Kim","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Colin-Lozano, B., Torres-Gomez, H., Hidalgo-Figueroa, S., Ch\u00e1vez-Silva, F., Estrada-Soto, S., Almanza-P\u00e9rez, J.C., and Navarrete-Vazquez, G. (2022). Synthesis, In Vitro, In Vivo and In Silico Antidiabetic Bioassays of 4-Nitro(thio)phenoxyisobutyric Acids Acting as Unexpected PPAR\u03b3 Modulators: An In Combo Study. Pharmaceuticals, 15.","DOI":"10.3390\/ph15010102"},{"key":"ref_23","first-page":"311","article-title":"Chemistory of Fibrates","volume":"1","author":"Balendiran","year":"2007","journal-title":"Curr. Chem. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1002\/cmdc.201900128","article-title":"Development of Fibrates as Important Scaffolds in Medicinal Chemistry","volume":"14","author":"Giampietro","year":"2019","journal-title":"ChemMedChem"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/jac\/49.1.103","article-title":"In vitro activity of nitazoxanide and related compounds against isolates of Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis","volume":"49","author":"Adagu","year":"2002","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.2165\/00003495-200767130-00015","article-title":"Nitazoxanide: A review of its use in the treatment of gastrointestinal infections","volume":"67","author":"Anderson","year":"2007","journal-title":"Drugs"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0377-1237(11)80020-1","article-title":"Nitazoxanide: A Broad Spectrum Antimicrobial","volume":"67","author":"Singh","year":"2011","journal-title":"Med. J. Armed Forces India"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e03721","DOI":"10.1002\/adhm.202503721","article-title":"Strategies to Improve the Lipophilicity of Hydrophilic Macromolecular Drugs","volume":"15","author":"Lindner","year":"2026","journal-title":"Adv. Healthc. Mater."},{"key":"ref_29","unstructured":"Li, D., and Kerns, E.H. (2016). Chapter 10\u2014Blood-Brain Barrier, Drug-Like Properties, Academic Press. [2nd ed.]."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/nature09524","article-title":"Integrating carbon-halogen bond formation into medicinal plant metabolism","volume":"468","author":"Runguphan","year":"2010","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Benedetto, T.D., Bagnoli, L., Rosati, O., Marini, F., Sancineto, L., and Santi, C. (2022). New Halo-gen-Containing Drugs Approved by FDA in 2021: An Overview on Their Syntheses and Pharmaceutical Use. Molecules, 27.","DOI":"10.3390\/molecules27051643"},{"key":"ref_32","first-page":"659","article-title":"Improvement of the Selectivity Index (SI) and Cytotoxicity Activity of Doxorubicin Drug by Panax ginseng Plant Extract","volume":"76","year":"2021","journal-title":"Arch. Razi Inst."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Pe\u00f1a-Mor\u00e1n, O.A., Villarreal, M.L., \u00c1lvarez-Berber, L., Meneses-Acosta, A., and Rodr\u00edguez-L\u00f3pez, V. (2016). Cytotoxicity, Post-Treatment Recovery, and Selectivity Analysis of Naturally Occurring Podophyllotoxins from Bursera fagaroides var. fagaroides on Breast Cancer Cell Lines. Molecules, 21.","DOI":"10.3390\/molecules21081013"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.exppara.2019.02.013","article-title":"Efficacy of lapachol on treatment of cutaneous and visceral leishmaniasis","volume":"199","author":"Alves","year":"2019","journal-title":"Exp. Parasitol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"824","DOI":"10.1002\/prot.20097","article-title":"An unusual triosephosphate isomerase from the early divergent eukaryote Giardia lamblia","volume":"55","author":"Cabrera","year":"2004","journal-title":"Proteins"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4859","DOI":"10.1074\/jbc.M609534200","article-title":"Characterization, kinetics, and crystal structures of fructose-1,6-bisphosphate aldolase from the human parasite, Giardia lamblia","volume":"282","author":"Galkin","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e0002419","DOI":"10.1128\/CMR.00024-19","article-title":"Giardia duodenalis: Biology and Pathogenesis","volume":"34","author":"Adam","year":"2021","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"980829","DOI":"10.1155\/2012\/980829","article-title":"Reconstruction of Sugar Metabolic Pathways of Giardia lamblia","volume":"2012","author":"Han","year":"2012","journal-title":"Int. J. Proteom."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Morales-Luna, L., Serrano-Posada, H., Gonz\u00e1lez-Valdez, A., Ortega-Cuellar, D., Vanoye-Carlo, A., Hern\u00e1ndez-Ochoa, B., Sierra-Palacios, E., Rufino-Gonz\u00e1lez, Y., Castillo-Rodr\u00edguez, R.A., and de la Cruz, V.P. (2018). Biochemical Characterization and Structural Modeling of Fused Glucose-6-Phosphate Dehydrogenase-Phosphogluconolactonase from Giardia lamblia. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092518"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"111383","DOI":"10.1016\/j.molbiopara.2021.111383","article-title":"Cloning, purification, and characterization of the 6-phosphogluconate dehydrogenase (6 PGDH) from Giardia lamblia","volume":"244","year":"2021","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_41","first-page":"11","article-title":"The pentose phosphate pathway and parasitic protozoa","volume":"13","author":"Barrett","year":"1997","journal-title":"Parasitol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/S0020-7519(01)00155-2","article-title":"Enzymes of carbohydrate metabolism as potential drug targets","volume":"31","author":"Opperdoes","year":"2001","journal-title":"Int. J. Parasitol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Morales-Luna, L., V\u00e1zquez-Bautista, M., Mart\u00ednez-Rosas, V., Rojas-Alarc\u00f3n, M.A., Ortega-Cuellar, D., Gonz\u00e1lez-Valdez, A., P\u00e9rez de la Cruz, V., Arreguin-Espinosa, R., Rodr\u00edguez-Bustamante, E., and Rodr\u00edguez-Flores, E. (2024). Fused Enzyme Glucose-6-Phosphate Dehydrogenase::6-Phosphogluconolactonase (G6PD::6PGL) as a Potential Drug Target in Giardia lamblia, Trichomonas vaginalis, and Plasmodium falciparum. Microorganisms, 12.","DOI":"10.3390\/microorganisms12010112"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s10930-015-9643-9","article-title":"Cloning, Expression and Characterization of Recombinant, NADH Oxidase from Giardia lamblia","volume":"35","year":"2016","journal-title":"Protein J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.molbiopara.2015.12.002","article-title":"Antioxidant defence systems in the protozoan pathogen Giardia intestinalis","volume":"206","author":"Mastronicola","year":"2016","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_46","first-page":"1","article-title":"The structural organization of Giardia intestinalis cytoskeleton","volume":"107","author":"Gadelha","year":"2020","journal-title":"Adv. Parasitol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez-Rosas, V., Hern\u00e1ndez-Ochoa, B., Morales-Luna, L., Ortega-Cuellar, D., Gonz\u00e1lez-Valdez, A., Arreguin-Espinosa, R., Rufino-Gonz\u00e1lez, Y., Calder\u00f3n-Jaimes, E., Castillo-Rodr\u00edguez, R.A., and Wong-Baeza, C. (2023). Nitazoxanide Inhibits the Bifunctional Enzyme GlG6PD::6PGL of Giardia lamblia: Biochemical and In Silico Characterization of a New Druggable Target. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411516"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1007\/s00436-002-0754-9","article-title":"Nitroheterocyclic drugs with broad spectrum activity","volume":"90","author":"Raether","year":"2003","journal-title":"Parasitol. Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1128\/AAC.01159-06","article-title":"Antiparasitic drug nitazoxanide inhibits the pyruvate oxidoreductases of Helicobacter pylori, selected anaerobic bacteria and parasites, and Campylobacter jejuni","volume":"51","author":"Hoffman","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1093\/jac\/dkr192","article-title":"Pyruvate:Ferredoxin oxidoreductase and thioredoxin reductase are involved in 5-nitroimidazole activation while flavin metabolism is linked to 5-nitroimidazole resistance in Giardia lamblia","volume":"66","author":"Leitsch","year":"2011","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1002\/pro.3691","article-title":"An overview of structure, function, and regulation of pyruvate kinases","volume":"28","author":"Schormann","year":"2019","journal-title":"Protein Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.bbrc.2007.12.139","article-title":"The catalyzing role of PPDK in Giardia lamblia","volume":"367","author":"Feng","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Ochoa, B., G\u00f3mez-Manzo, S., S\u00e1nchez-Carrillo, A., Marcial-Quino, J., Rocha-Ram\u00edrez, L.M., Santos-Segura, A., Ram\u00edrez-Nava, E.J., Arreguin-Espinosa, R., Cuevas-Cruz, M., and M\u00e9ndez-Tenorio, A. (2020). Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds. Molecules, 25.","DOI":"10.3390\/molecules25173979"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.gene.2016.01.018","article-title":"Validation of housekeeping genes as an internal control for gene expression studies in Giardia lamblia using quantitative real-time PCR","volume":"581","author":"Fierro","year":"2016","journal-title":"Gene"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"519","DOI":"10.3855\/jidc.5768","article-title":"Determination of PFOR gene expression in strains of G. intestinalis with different inhibitory concentrations of metronidazole","volume":"9","author":"Begaydarova","year":"2015","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez-Cardona, J.Y., Calder\u00f3n-Jaimes, E., Ortega-Cuellar, D., S\u00e1nchez-Carrillo, A., Castillo-Rodr\u00edguez, R.A., Canseco-\u00c1vila, L.M., Rocha-Ram\u00edrez, L.M., Mart\u00ednez-Rosas, V., G\u00f3mez-Manzo, S., and Hern\u00e1ndez-Ochoa, B. (2024). Effect of Trichomonacide 6-Nitro-1H-benzimidazole Derivative Compounds on Expression Level of Metabolic Genes in Trichomonas vaginalis. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25084568"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Ochoa, B., Mart\u00ednez-Rosas, V., Morales-Luna, L., Calder\u00f3n-Jaimes, E., Rocha-Ram\u00edrez, L.M., Ortega-Cuellar, D., Rufino-Gonz\u00e1lez, Y., Gonz\u00e1lez-Valdez, A., Arreguin-Espinosa, R., and Enr\u00edquez-Flores, S. (2022). Pyridyl Methylsulfinyl Benzimidazole Derivatives as Promising Agents against Giardia lamblia and Trichomonas vaginalis. Molecules, 27.","DOI":"10.3390\/molecules27248902"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/s41592-022-01685-y","article-title":"AlphaFill: Enriching AlphaFold models with ligands and cofactors","volume":"20","author":"Hekkelman","year":"2023","journal-title":"Nat. Methods"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s13321-021-00522-2","article-title":"GNINA 1.0: Molecular docking with deep learning","volume":"3","author":"McNutt","year":"2021","journal-title":"J. Cheminform."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"9388","DOI":"10.1021\/acs.jcim.4c01429","article-title":"CACHE Challenge #1: Docking with GNINA Is All You Need","volume":"64","author":"Dunn","year":"2024","journal-title":"J. Chem. Inf. Model."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13321-025-00973-x","article-title":"GNINA 1.3: The next increment in molecular docking with deep learning","volume":"17","author":"McNutt","year":"2025","journal-title":"J. Cheminform."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1021\/ct100578z","article-title":"PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKa Predictions","volume":"7","author":"Olsson","year":"2011","journal-title":"J. Chem. Theory Comput."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"11225","DOI":"10.1021\/ja9621760","article-title":"Development and Testing of the OPLS All-Atom Force Field on Conformational Energetics and Properties of Organic Liquids","volume":"118","author":"Jorgensen","year":"1996","journal-title":"J. Am. Chem. Soc."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/17\/2980\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:21:57Z","timestamp":1787890917000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/17\/2980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":64,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["molecules31172980"],"URL":"https:\/\/doi.org\/10.3390\/molecules31172980","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}