{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T23:33:55Z","timestamp":1776814435431,"version":"3.51.2"},"reference-count":26,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EU"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In the present study, we assess tyrosol derivatives bearing 3,5-disubstituted isoxazoles and 1,4-disubstituted triazoles for their ability to inhibit the proliferation of K562 cells derived from leukemia as well as primary chronic myeloid leukemia (CML) cells obtained from the peripheral blood of 15 CML patients including 10 patients with untreated chronic phase and 5 patients with resistance against imatinib or multiple TKI. Our results showed that most derivatives displayed significant anti-proliferative activity against K562 cells in a dose-dependent manner. Among them, compounds 3d and 4a exhibited greater potent anticancer activity with respective IC50 values of 16 and 18 \u00b5g\/mL (45 \u00b5M and 61 \u00b5M). Interestingly, compound 3d inhibited CML cell proliferation not only in newly diagnosed but also in imatinib-resistant patients. We demonstrated that the anti-proliferative effect of this compound is mediated by a pro-apoptotic activity by promoting oxidative stress and modulating the activity of the Akt, p38 MAPK and Erk 1\/2 pathways. In conclusion, our data highlight the potential of this class of derivative as a novel promising therapeutic agent for CML therapy.<\/jats:p>","DOI":"10.3390\/molecules27165086","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T05:43:57Z","timestamp":1660196637000},"page":"5086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Tyrosol Derivatives, Bearing 3,5-Disubstituted Isoxazole and 1,4-Disubstituted Triazole, as Potential Antileukemia Agents by Promoting Apoptosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Zaineb","family":"Abdelkafi-Koubaa","sequence":"first","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imen","family":"Aissa","sequence":"additional","affiliation":[{"name":"Team Medicinal Chemistry and Natural Products (LR11ES39), Laboratory of Heterocyclic, Chemistry, Natural Products and Reactivity, Department of Chemistry, Faculty of Science of Monastir, University of Monastir, Monastir 5019, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5858-1803","authenticated-orcid":false,"given":"Hichem","family":"Ben Jannet","sequence":"additional","affiliation":[{"name":"Team Medicinal Chemistry and Natural Products (LR11ES39), Laboratory of Heterocyclic, Chemistry, Natural Products and Reactivity, Department of Chemistry, Faculty of Science of Monastir, University of Monastir, Monastir 5019, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najet","family":"Srairi-Abid","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naziha","family":"Marrakchi","sequence":"additional","affiliation":[{"name":"Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"},{"name":"Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1068, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4897-1925","authenticated-orcid":false,"given":"Samia","family":"Menif","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Hematology Laboratory, LR16IPT07, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, Tunisia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1016\/j.drudis.2019.05.007","article-title":"Current outlook on drug resistance in chronic myeloid leukemia (CML) and potential therapeutic options","volume":"24","author":"Jiang","year":"2019","journal-title":"Drug Discov. 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