{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:47:39Z","timestamp":1790038059631,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["309522\/2023\u20104"],"award-info":[{"award-number":["309522\/2023\u20104"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Betulinic acid (BA) has been described with several therapeutic properties, including anticancer, anti\u2010inflammatory, antibacterial, antiviral, antidiabetic, antimalarial, and anti\u2010HIV activities. Unfortunately, the long\u2010term use of BA can cause mild toxicity in users, which may be solved by modifying its chemical structure to obtain BA derivatives. As proposed in the present study, the influence on the toxicity profile of the modification at carbon\u20103 of BA was evaluated by the replacement of the hydroxyl group with oxime and amine, resulting in derivatives with good yields. These derivatives were previously described by our group and showed better antileukemic activity than BA. Hence, toxicity assays were considered by assessing in\u00a0vivo using\n                    <jats:italic>Galleria mellonella<\/jats:italic>\n                    and murine models in accordance with the Organization for Economic Co\u2010Operation and Development (OECD) guidelines (Guideline). Hematological and histological analyses were performed to obtain additional toxicity data. Acute toxicological studies revealed the low toxicity of the BA derivatives 3 (oxime) and 4 (amine) in the\n                    <jats:italic>G. mellonella<\/jats:italic>\n                    model, according to the Global Harmonising System of Classification and Labeling of Chemicals (GHS) classification. In the murine model, BA derivative 3 (oxime) was classified as Class 5 (LD\n                    <jats:sub>50<\/jats:sub>\n                    \u2009&gt;\u20092000\u2009mg\/kg), and BA derivative 4 (amine) as Class 4 (LD\n                    <jats:sub>50<\/jats:sub>\n                    \u2009&gt;\u2009300\u20132000\u2009mg\/kg). No significant changes in the relative mass of organs (except to the spleen for BA derivative 3 [oxime] group; 2000\u2009mg\/kg), histology, or hematological parameters were observed. These findings indicate that chemical structure modification provides derivatives exhibiting a safe profile with advances in their pharmacological properties, as already described.\n                  <\/jats:p>","DOI":"10.1002\/jat.70040","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T03:06:09Z","timestamp":1765767969000},"page":"2448-2456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Acute Toxicological Evaluation in Alternative Method\n                    <i>Galleria mellonella<\/i>\n                    and Murine Models of the Betulinic Acid Derivatives"],"prefix":"10.1002","volume":"46","author":[{"given":"Elenilson\u00a0F.","family":"Silva","sequence":"first","affiliation":[{"name":"Laboratory of Phytochemistry and Organic Synthesis, Department of Raw Material Production Federal University of Rio Grande do Sul  Porto Alegre 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