{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T14:03:27Z","timestamp":1768745007061,"version":"3.49.0"},"reference-count":59,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Comisi\u00f3n de Operaci\u00f3n y Fomento de Actividades Acad\u00e9micas and Secretar\u00eda de Investigaci\u00f3n y Posgrado del Instituto Polit\u00e9cnico Nacional","award":["20230846"],"award-info":[{"award-number":["20230846"]}]},{"name":"Comisi\u00f3n de Operaci\u00f3n y Fomento de Actividades Acad\u00e9micas and Secretar\u00eda de Investigaci\u00f3n y Posgrado del Instituto Polit\u00e9cnico Nacional","award":["MULTI20210729"],"award-info":[{"award-number":["MULTI20210729"]}]},{"name":"Comisi\u00f3n de Operaci\u00f3n y Fomento de Actividades Acad\u00e9micas and Secretar\u00eda de Investigaci\u00f3n y Posgrado del Instituto Polit\u00e9cnico Nacional","award":["254600"],"award-info":[{"award-number":["254600"]}]},{"name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas","award":["20230846"],"award-info":[{"award-number":["20230846"]}]},{"name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas","award":["MULTI20210729"],"award-info":[{"award-number":["MULTI20210729"]}]},{"name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas","award":["254600"],"award-info":[{"award-number":["254600"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Valproic acid (VPA) is a drug that has various therapeutic applications; however, it has been associated with liver damage. Furthermore, it is interesting to propose new compounds derived from VPA as N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA has better antiproliferative activity than the VPA in different cancer cell lines. The purpose of this study was to evaluate the liver injury of HO-AAVPA by acute treatment (once administration) and repeated doses for 7 days under intraperitoneal administration. The median lethal dose value (LD50) was determined in rats and mice (females and males) using OECD Guideline 425. In the study, male rats were randomly divided into 4 groups (n = 7), G1: control (without treatment), G2: vehicle, G3: VPA (500 mg\/kg), and G4: HO-AAVPA (708 mg\/kg, in equimolar ratio to VPA). Some biomarkers related to hepatotoxicity were evaluated. In addition, macroscopic and histological studies were performed. The LD50 value of HO-AAVPA was greater than 2000 mg\/kg. Regarding macroscopy and biochemistry, the HO-AAVPA does not induce liver injury according to the measures of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, glutathione peroxidase, glutathione reductase, and catalase activities. Comparing the treatment with HO-AAVPA and VPA did not show a significant difference with the control group, while malondialdehyde and glutathione-reduced levels in the group treated with HO-AAVPA were close to those of the control (p \u2264 0.05). The histological study shows that liver lesions caused by HO-AAVPA were less severe compared with VPA. Therefore, it is suggested that HO-AAVPA does not induce hepatotoxicity at therapeutic doses, considering that in the future it could be proposed as an antineoplastic drug.<\/jats:p>","DOI":"10.3390\/molecules28176282","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T06:10:22Z","timestamp":1693203022000},"page":"6282","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hepatotoxic Evaluation of N-(2-Hydroxyphenyl)-2-Propylpentanamide: A Novel Derivative of Valproic Acid for the Treatment of Cancer"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3158-9240","authenticated-orcid":false,"given":"Ana Mar\u00eda","family":"Correa Basurto","sequence":"first","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tomas, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3897-6477","authenticated-orcid":false,"given":"Feliciano","family":"Tamay Cach","sequence":"additional","affiliation":[{"name":"Laboratorio de Investigaci\u00f3n de Bioqu\u00edmica Aplicada, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tomas, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0467-2528","authenticated-orcid":false,"given":"Rosa Adriana","family":"Jarillo Luna","sequence":"additional","affiliation":[{"name":"Laboratorio de Morfolog\u00eda, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tomas, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2781-551X","authenticated-orcid":false,"given":"Laura Cristina","family":"Cabrera P\u00e9rez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tomas, Ciudad de M\u00e9xico 11340, Mexico"},{"name":"Laboratorio de Farmacolog\u00eda, Departamento de Bioprocesos, Unidad Profesional Interdisciplinaria de Biotecnolog\u00eda, Instituto Polit\u00e9cnico Nacional, Avenida Acueducto s\/n, La Laguna Ticoman, Ciudad de M\u00e9xico 07340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-5265","authenticated-orcid":false,"given":"Jos\u00e9","family":"Correa Basurto","sequence":"additional","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tomas, Ciudad de M\u00e9xico 11340, Mexico"},{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos e Innovaci\u00f3n Biotecnol\u00f3gica, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tomas, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2976-1877","authenticated-orcid":false,"given":"Fernando","family":"Garc\u00eda Dolores","sequence":"additional","affiliation":[{"name":"Laboratorio de Patolog\u00eda, Instituto de Ciencias Forenses de la Ciudad de M\u00e9xico, Av. Ni\u00f1os H\u00e9roes 130. Col. Doctores, Delegaci\u00f3n Cuauht\u00e9moc, Ciudad de M\u00e9xico 06720, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2471-9875","authenticated-orcid":false,"given":"Jessica Elena","family":"Mendieta Wejebe","sequence":"additional","affiliation":[{"name":"Laboratorio de Biof\u00edsica y Biocat\u00e1lisis, Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y Salvador D\u00edaz Mir\u00f3n s\/n, Casco de Santo Tomas, Ciudad de M\u00e9xico 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"key":"ref_1","unstructured":"P\u00e9rez-Gonz\u00e1lez, O.A., Bermudez-Lugo, J.A., Correa-Basurto, J., Vasquez-Moctezuma, I., Padilla-Mart\u00ednez, I.I., and Trujillo-Ferrara, J.G. (2019). 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