{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:04:25Z","timestamp":1787774665597,"version":"build-2784847793"},"reference-count":31,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"This research was funded by Fondos Federales, M\u00e9xico. B.H.-O was funded by HIM\/2017\/100 SSA 1430 and L.M.R.-R by HIM\/2014\/013 SSA 1120, and by the E022 Program, National Institute of Pediatrics, Mexico City, Mexico (Recursos Fiscales para la Investigaci\u00f3n","award":["S.G.-M. was supported by INP 038\/2019. J.M.-Q. was supported by INP 024\/2017, and by CONACYT grant 259201, C\u00e1tedras CONACYT (2184) project number 2057."],"award-info":[{"award-number":["S.G.-M. was supported by INP 038\/2019. J.M.-Q. was supported by INP 024\/2017, and by CONACYT grant 259201, C\u00e1tedras CONACYT (2184) project number 2057."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Giardiasis is a diarrheal disease that is highly prevalent in developing countries. Several drugs are available for the treatment of this parasitosis; however, failures in drug therapy are common, and have adverse effects and increased resistance of the parasite to the drug, generating the need to find new alternative treatments. In this study, we synthesized a series of 2-mercaptobenzimidazoles that are derivatives of omeprazole, and the chemical structures were confirmed through mass, 1H NMR, and 13C NMR techniques. The in vitro efficacy compounds against Giardia, as well as its effect on the inhibition of triosephosphate isomerase (TPI) recombinant, were investigated, the inactivation assays were performed with 0.2 mg\/mL of the enzyme incubating for 2 h at 37 \u00b0C in TE buffer, pH 7.4 with increasing concentrations of the compounds. Among the target compounds, H-BZM2, O2N-BZM7, and O2N-BZM9 had greater antigiardial activity (IC50: 36, 14, and 17 \u00b5M on trophozoites), and inhibited the TPI enzyme (K2: 2.3, 3.2, and 2.8 M\u22121 s\u22121) respectively, loading alterations on the secondary structure, global stability, and tertiary structure of the TPI protein. Finally, we demonstrated that it had low toxicity on Caco-2 and HT29 cells. This finding makes it an attractive potential starting point for new antigiardial drugs.<\/jats:p>","DOI":"10.3390\/molecules25173979","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T14:21:10Z","timestamp":1598970070000},"page":"3979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3939-6930","authenticated-orcid":false,"given":"Beatriz","family":"Hern\u00e1ndez-Ochoa","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunoqu\u00edmica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud, Ciudad de Mexico 06720, 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, Ciudad de M\u00e9xico 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adri\u00e1n","family":"S\u00e1nchez-Carrillo","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunoqu\u00edmica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud, Ciudad de Mexico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4591-7379","authenticated-orcid":false,"given":"Jaime","family":"Marcial-Quino","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Ciencia y Tecnolog\u00eda (CONACYT), Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Ciudad de Mexico 04530, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7204-1421","authenticated-orcid":false,"given":"Luz Mar\u00eda","family":"Rocha-Ram\u00edrez","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Enfermedades Infecciosas, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud Dr. M\u00e1rquez No. 162, Col Doctores, Delegaci\u00f3n Cuauht\u00e9moc, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Araceli","family":"Santos-Segura","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunoqu\u00edmica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud, Ciudad de Mexico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1166-190X","authenticated-orcid":false,"given":"Edson Jiovany","family":"Ram\u00edrez-Nava","sequence":"additional","affiliation":[{"name":"Laboratorio de Bioqu\u00edmica Gen\u00e9tica, Instituto Nacional de Pediatr\u00eda, Secretar\u00eda de Salud, Ciudad de M\u00e9xico 04530, 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 Mexico, Ciudad de Mexico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-5930","authenticated-orcid":false,"given":"Miguel","family":"Cuevas-Cruz","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica de Biomacromol\u00e9culas, Instituto de Qu\u00edmica, Universidad Nacional Aut\u00f3noma de Mexico, Ciudad de Mexico 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1871-4311","authenticated-orcid":false,"given":"Alfonso","family":"M\u00e9ndez-Tenorio","sequence":"additional","affiliation":[{"name":"Laboratorio de Biotecnolog\u00eda y Bioinform\u00e1tica Gen\u00f3mica, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Calder\u00f3n-Jaimes","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunoqu\u00edmica, Hospital Infantil de M\u00e9xico Federico G\u00f3mez, Secretar\u00eda de Salud, Ciudad de Mexico 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/S0140-6736(02)07744-9","article-title":"Effects of stunting, diarrhoeal disease, and parasitic infection during infancy on cognition in late childhood: A follow-up study","volume":"359","author":"Berkman","year":"2002","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1080\/1040-840291046713","article-title":"Current trends in research into the waterborne parasite giardia","volume":"28","author":"Lane","year":"2002","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.ijheh.2010.06.005","article-title":"Giardia taxonomy, phylogeny and epidemiology: Facts and open questions","volume":"213","author":"Plutzer","year":"2010","journal-title":"Int. J. Hyg. Environ. Health"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Savioli, L., Engels, D., Daumerie, D., Jannin, J., Alvar, J., Asiedu, K., Gastellu-Etchegorry, M., Simarro, P., and Mariotti, S.P. (2006). Response from savioli and colleagues from the Department of Neglected Tropical Diseases, World Health Organization. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030283"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1128\/CMR.14.1.114-128.2001","article-title":"Treatment of giardiasis","volume":"14","author":"Gardner","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1179\/136485908X267894","article-title":"The treatment of giardiasis in children: Single-dose tinidazole compared with 3 days of nitazoxanide","volume":"102","author":"Escobedo","year":"2008","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7303","DOI":"10.1128\/AAC.03834-14","article-title":"Discovery of novel antigiardiasis drug candidates","volume":"58","author":"Kulakova","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1128\/CMR.14.1.150-164.2001","article-title":"Drug targets and mechanisms of resistance in the Anaerobic Protozoa","volume":"14","author":"Upcroft","year":"2001","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1016\/j.biotechadv.2015.04.009","article-title":"Drug resistance in Giardia duodenalis","volume":"33","author":"Ansell","year":"2015","journal-title":"Biotechnol. Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ijpddr.2018.04.008","article-title":"Physiological aspects of nitro drug resistance in Giardia lamblia","volume":"8","author":"Muller","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bbagen.2015.10.021","article-title":"Proton pump inhibitors drastically modify triosephosphate isomerase from Giardia lamblia at functional and structural levels, providing molecular leads in the design of new antigiardiasic drugs","volume":"1860","year":"2016","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1002\/prot.23100","article-title":"Determining the molecular mechanism of inactivation by chemical modification of triosephosphate isomerase from the human parasite Giardia lamblia: A study for antiparasitic drug design","volume":"79","year":"2011","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7380","DOI":"10.1016\/j.bmc.2010.09.019","article-title":"Towards a systematic characterization of the antiprotozoal activity landscape of benzimidazole derivatives","volume":"18","author":"Santos","year":"2010","journal-title":"Bioorganic Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7351","DOI":"10.1016\/j.bmcl.2011.10.028","article-title":"Antiprotozoal activity of proton-pump inhibitors","volume":"21","author":"Castillo","year":"2011","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S157","DOI":"10.1016\/j.arabjc.2012.07.017","article-title":"Benzimidazoles: A biologically active compounds","volume":"10","author":"Salahuddin","year":"2017","journal-title":"Arab. J. Chem."},{"key":"ref_17","first-page":"1","article-title":"Novel giardicidal compounds bearing proton pump inhibitor scaffold proceeding through triosephosphate isomerase inactivation","volume":"7","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0960-894X(00)00619-3","article-title":"Synthesis and antiparasitic activity of 2-(Trifluoromethyl)benzimidazole derivatives","volume":"11","author":"Cedillo","year":"2001","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1016\/S0960-894X(02)00346-3","article-title":"Synthesis and antiparasitic activity of 1H-benzimidazole derivatives","volume":"12","author":"Valdez","year":"2002","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4221","DOI":"10.1016\/j.bmcl.2013.05.012","article-title":"Synthesis and antiprotozoal activity of novel 2-{[2-(1H-imidazol-1-yl)ethyl]sulfanyl}-1H-benzimidazole derivatives","volume":"23","author":"Castillo","year":"2013","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7072","DOI":"10.1128\/AAC.02900-14","article-title":"Giardial triosephosphate isomerase as possible target of the cytotoxic effect of omeprazole in Giardia lamblia","volume":"58","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_22","first-page":"1","article-title":"On the molecular and cellular effects of omeprazole to further support its effectiveness as an antigiardial drug","volume":"9","author":"Ridaura","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_23","unstructured":"Constansa, J.F., Pinol, A.C., and Corominas, J.P. (1988). 2-Benzimidazolylalkylthio (or -sulfinyl or -sulfonyl) Derivatives, Their Preparation and Their Application as Medicinal Products. (US4791114A), U.S. Patent."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.1016\/j.tetlet.2011.08.033","article-title":"An efficient synthesis of dexlansoprazole employing asymmetric oxidation strategy","volume":"52","author":"Raju","year":"2011","journal-title":"Tetrahedron Lett."},{"key":"ref_25","unstructured":"Jang, S.-Y.K., Tai Won, K., Sungbum, K., Byung-Ku, C., Chang-Ju, K., Cheol Kyung, H., Tae Hee, S., Kwee Hyun, L., and Gwan, S. (2010). Process for Preparing (r)-(+)-Lansoprazole and Intermediate Used Therein. (Patent Cooperation Treaty (PCT) WO2010068049A2)."},{"key":"ref_26","unstructured":"Liqiang, Y., Chunzhen, H., Zhihong, L., Yuanyuan, H., and Xiangan, M. (2017). A Kind of R-Lansoprazole and Preparation Method Thereof and Purposes. (CN106946849A)."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8591","DOI":"10.1038\/s41598-018-26845-z","article-title":"First characterization of a microsporidial triosephosphate isomerase and the biochemical mechanisms of its inactivation to propose a new druggable target","volume":"8","author":"Nava","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez-Alc\u00e1ntara, G., Torres-Larios, A., Enr\u00edquez-Flores, S., Garc\u00eda-Torres, I., Castillo-Villanueva, A., M\u00e9ndez, S.-T., de la Mora, I., G\u00f3mez-Manzo, S., Torres-Arroyo, A., and L\u00f3pez-Vel\u00e1zquez, G. (2013). Structural and functional perturbation of Giardia lamblia triosephosphate isomerase by modification of a non-catalytic, non-conserved region. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069031"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/pro.3289","article-title":"PDBsum: Structural summaries of PDB entries","volume":"27","author":"Laskowski","year":"2017","journal-title":"Protein Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"W270","DOI":"10.1093\/nar\/gkr366","article-title":"SwissDock, a protein-small molecule docking web service based on EADock DSS","volume":"39","author":"Grosdidier","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/17\/3979\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:05:23Z","timestamp":1760177123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/17\/3979"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":31,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["molecules25173979"],"URL":"https:\/\/doi.org\/10.3390\/molecules25173979","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,1]]}}}