{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:04:23Z","timestamp":1787774663599,"version":"build-2784847793"},"reference-count":68,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T00:00:00Z","timestamp":1746662400000},"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 (Recursos Fiscales para la Investigaci\u00f3n)","award":["INP 021\/2022"],"award-info":[{"award-number":["INP 021\/2022"]}]},{"name":"E022 Program, National Institute of Pediatrics, Mexico City, Mexico (Recursos Fiscales para la Investigaci\u00f3n)","award":["HIM\/2019\/036 SSA. 1595"],"award-info":[{"award-number":["HIM\/2019\/036 SSA. 1595"]}]},{"name":"E022 Program, National Institute of Pediatrics, Mexico City, Mexico (Recursos Fiscales para la Investigaci\u00f3n)","award":["CF-2023-I-811"],"award-info":[{"award-number":["CF-2023-I-811"]}]},{"name":"Fondos Federales","award":["INP 021\/2022"],"award-info":[{"award-number":["INP 021\/2022"]}]},{"name":"Fondos Federales","award":["HIM\/2019\/036 SSA. 1595"],"award-info":[{"award-number":["HIM\/2019\/036 SSA. 1595"]}]},{"name":"Fondos Federales","award":["CF-2023-I-811"],"award-info":[{"award-number":["CF-2023-I-811"]}]},{"name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas (CONAHCYT) Ciencia de Frontera 2023","award":["INP 021\/2022"],"award-info":[{"award-number":["INP 021\/2022"]}]},{"name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas (CONAHCYT) Ciencia de Frontera 2023","award":["HIM\/2019\/036 SSA. 1595"],"award-info":[{"award-number":["HIM\/2019\/036 SSA. 1595"]}]},{"name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas (CONAHCYT) Ciencia de Frontera 2023","award":["CF-2023-I-811"],"award-info":[{"award-number":["CF-2023-I-811"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Giardiasis is a common intestinal infection caused by Giardia lamblia. The standard treatment for this parasitic infection involves the administration of nitroimidazoles, albendazoles, and nitrothiazoles. However, in recent years, Giardia lamblia strains resistant to these treatments have been reported. Additionally, the current therapies exhibit considerable side effects, highlighting the need for new compounds that specifically target this parasite. The aim of this study was to evaluate nitrothiazole analogs and assess their impact on the metabolic, redox, and structural gene expression of this parasite. First, the compounds CNZ-7, CNZ-8, FLP-2, FLP-6, and FLP-8 were tested at concentrations ranging from 0 to 50 \u00b5M to determine their IC50 in G. lamblia cultures. Subsequently, gene expression changes and structural cell damage in trophozoites were analyzed following incubation with the IC50 of each compound. The giardicidal activity of the compounds was also evaluated in a nitazoxanide-resistant strain. The results showed that FLP-2, FLP-6, and FLP-8 exhibited a stronger effect on trophozoite viability compared to nitazoxanide (NTZ) and metronidazole (MTZ). Both compounds induced an increase in the expression of phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PK), pyruvate phosphate dikinase (PPDK), and pyruvate:ferredoxin oxidoreductase (PFOR). Additionally, FLP-2 caused ultrastructural alterations in trophozoites. Furthermore, FLP-2, FLP-6, and FLP-8 demonstrated efficacy against drug-resistant strains. These findings suggest that FLP-2, FLP-6, and FLP-8 are promising candidates for the treatment of giardiasis, as they effectively reduce parasite viability, modify gene expression, and exhibit activity against drug-resistant G. lamblia strains.<\/jats:p>","DOI":"10.3390\/ijms26104504","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T11:37:02Z","timestamp":1746704222000},"page":"4504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nitazoxanide Analogs: Synthesis, In Vitro Giardicidal Activity, and Effects on Giardia lamblia Metabolic Gene Expression"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7194-4522","authenticated-orcid":false,"given":"Laura","family":"Morales-Luna","sequence":"first","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"},{"name":"Posgrado en Ciencias Biol\u00f3gicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Hern\u00e1ndez-Ochoa","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunoqu\u00edmica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Gonz\u00e1lez-Valdez","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular y Biotecnolog\u00eda, Instituto de Investigaciones Biom\u00e9dicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4651-7892","authenticated-orcid":false,"given":"Montserrat","family":"V\u00e1zquez-Bautista","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"},{"name":"Programa de Posgrado en Biomedicina y Biotecnolog\u00eda Molecular, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, 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, Mexico City 04510, 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\/0000-0003-2058-5707","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"}]},{"given":"Elizabeth","family":"Hern\u00e1ndez-Urz\u00faa","sequence":"additional","affiliation":[{"name":"Laboratorio de Toxicolog\u00eda Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, 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, Boulevard de la Tecnolog\u00eda, 1036 Z-1, P 2\/2, Atlacholoaya 62790, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6580-3440","authenticated-orcid":false,"given":"Noem\u00ed","family":"C\u00e1rdenas-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Laboratorio de Neurociencias, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6137-6499","authenticated-orcid":false,"given":"V\u00edctor","family":"Mart\u00ednez-Rosas","sequence":"additional","affiliation":[{"name":"Departamento de Ingenier\u00eda Qu\u00edmica y Bioqu\u00edmica, Instituto Tecnol\u00f3gico de Milpa Alta, Tecnol\u00f3gico Nacional de M\u00e9xico, Milpa Alta, Mexico City 12300, 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, Av. Universidad 1001, Chamilpa, Cuernavaca 62209, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-9182","authenticated-orcid":false,"given":"Sa\u00fal","family":"G\u00f3mez-Manzo","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1097\/QCO.0000000000000668","article-title":"Giardiasis treatment: An update with a focus on refractory disease","volume":"33","author":"Hanevik","year":"2020","journal-title":"Curr. Opin. Infect. 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