{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:51:53Z","timestamp":1762077113832,"version":"build-2065373602"},"reference-count":52,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,18]],"date-time":"2022-11-18T00:00:00Z","timestamp":1668729600000},"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"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Treatments to combat giardiasis have been reported to have several drawbacks, partly due to the drug resistance and toxicity of current antiparasitic agents. These constraints have prompted many researchers to investigate new drugs that act against protozoan parasites. Enzyme inhibition is an important means of regulating pathogen metabolism and has recently been identified as a significant alternative target in the search for new treatments. Glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase (G6PD::6PGL) is a bifunctional enzyme involved in the pentose phosphate pathway (PPP) in Giardia\u00a0lamblia (G. lamblia). The G. lamblia enzyme is unusual since, unlike the human enzyme, it is a fused enzyme. Here, we show, through inhibition assays, that an in-house chemical library of 120 compounds and four target compounds, named CNZ-7, CNZ-8, CMC-1, and FLP-2, are potent inhibitors of the G. lamblia G6PD::6PGL fused enzyme. With a constant (k2) of 2.3, 3.2, and 2.8 M\u22121 s\u22121, respectively, they provoke alterations in the secondary and tertiary protein structure and global stability. As a novel approach, target compounds show antigiardial activity, with IC50 values of 8.7, 15.2, 15.3, and 24.1 \u00b5M in trophozoites from G. lamblia. Moreover, these compounds show selectivity against G. lamblia, since, through counter-screening in Caco-2 and HT29 human cells, they were found to have low toxicity. This finding positions these compounds as a potential and attractive starting point for new antigiardial drugs.<\/jats:p>","DOI":"10.3390\/ijms232214358","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T02:52:21Z","timestamp":1668999141000},"page":"14358","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Giardia lamblia G6PD::6PGL Fused Protein Inhibitors Decrease Trophozoite Viability: A New Alternative against Giardiasis"],"prefix":"10.3390","volume":"23","author":[{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6137-6499","authenticated-orcid":false,"given":"V\u00edctor","family":"Mart\u00ednez-Rosas","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-4911","authenticated-orcid":false,"given":"Daniel","family":"Ortega-Cuellar","sequence":"additional","affiliation":[{"name":"Laboratorio de Nutrici\u00f3n Experimental, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-4482","authenticated-orcid":false,"given":"Yadira","family":"Rufino-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Laboratorio de Parasitolog\u00eda Experimental, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Mexico City 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6978-2176","authenticated-orcid":false,"given":"Adri\u00e1n Marcelo","family":"Franco-V\u00e1squez","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlos","family":"Mart\u00ednez-Conde","sequence":"additional","affiliation":[{"name":"Facultad de Farmacia, Universidad Aut\u00f3noma del Estado de Morelos, Av. Universidad 1001, Chamilpa, Cuernavaca 62209, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5694-3118","authenticated-orcid":false,"given":"Luis Miguel","family":"Canseco-\u00c1vila","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias Qu\u00edmicas, Campus IV, Universidad Aut\u00f3noma de Chiapas, Tapachula City 30700, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5050-2143","authenticated-orcid":false,"given":"Fernando","family":"G\u00f3mez-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Laboratorio de Enfermedades Osteoarticulares e Inmunol\u00f3gicas, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Nacional de Medicina y Homeopat\u00eda, Instituto Polit\u00e9cnico Nacional, Mexico City 07320, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,18]]},"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":"Morch","year":"2020","journal-title":"Curr. 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