{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:39:23Z","timestamp":1786714763976,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004410","name":"Scientific and Technological Research Council of Turkey","doi-asserted-by":"publisher","award":["123Z040"],"award-info":[{"award-number":["123Z040"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"award":["123Z040"],"award-info":[{"award-number":["123Z040"]}],"id":[{"id":"https:\/\/ror.org\/04w9kkr77","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Background: Chronic myeloid leukemia (CML) and other leukemia subtypes remain significant hematological malignancies that require the development of novel therapeutic agents with improved efficacy and selectivity. This study aimed to design, synthesize, and evaluate novel oleanolic acid (OA) derivatives as potential anti-leukemic agents. Methods: Structural modifications at the C-28 position afforded halogenated benzyl ester derivatives (MT-A\u2013D), while aromatic acyl substitutions at the C-3 position generated derivatives NOA-1\u201316. The cytotoxic effects of the synthesized compounds were evaluated against K562, HL-60, Jurkat, and MT-2 leukemia cell lines and healthy PBMCs using the MTT assay. Apoptosis induction and ABL tyrosine kinase (TK) inhibition were also investigated. Molecular docking, MM\/GBSA binding free energy calculations, and molecular dynamics (MD) simulations were performed to characterize ligand-enzyme interactions and binding stability. Results: MT-A exhibited the highest activity against HL-60 cells (IC50 = 4.17 \u00b1 0.65 \u03bcM), surpassing imatinib (IC50 = 13.34 \u00b1 1.92 \u03bcM). NOA-8 was the most potent compound against Jurkat and MT-2 cells, with IC50 values of 6.81 \u00b1 1.08 \u03bcM and 2.48 \u00b1 0.88 \u03bcM, respectively. MT-A, MT-C, NOA-3, and NOA-8 displayed IC50 values above 300 \u03bcM in PBMCs, indicating favorable selectivity. MT-A and MT-C induced significant apoptosis in K562 cells, while kinase assays revealed moderate ABL TK inhibition by these compounds. Docking, MM\/GBSA, and MD analyses supported stable binding of MT-A and MT-C within the ABL ATP-binding pocket. Conclusions: MT-A, MT-C, NOA-3, and particularly NOA-8 emerged as promising anti-leukemic lead compounds with potent antiproliferative activity and favorable selectivity profiles, warranting further investigation for leukemia therapy.<\/jats:p>","DOI":"10.3390\/life16081335","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:12:56Z","timestamp":1786713176000},"page":"1335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis and Biological Evaluation of Novel Oleanolic Acid Derivatives as Potential Anti-Leukemic Agents"],"prefix":"10.3390","volume":"16","author":[{"given":"Nefise","family":"Demir","sequence":"first","affiliation":[{"name":"Department of Nanoscience and Nanotechnology, Izmir K\u00e2tip Celebi University, Izmir 35620, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9796-7669","authenticated-orcid":false,"given":"Halilibrahim","family":"Ciftci","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Burdur Mehmet Akif Ersoy University, Istiklal Campus, Burdur 15200, T\u00fcrkiye"},{"name":"Medicinal and Biological Chemistry Science Farm Joint Research Laboratory, Faculty of Life Sciences, Kumamoto University, Kumamoto 862-0973, Japan"},{"name":"Department of Drug Discovery, Science Farm Ltd., Kumamoto 862-0976, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9555-1814","authenticated-orcid":false,"given":"Khaled M.","family":"Elamin","sequence":"additional","affiliation":[{"name":"Global Center for Natural Products Research, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1749-8293","authenticated-orcid":false,"given":"Mustafa","family":"Can","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Sciences, Faculty of Engineering and Architecture, Izmir K\u00e2tip Celebi University, Izmir 35620, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4847-9711","authenticated-orcid":false,"given":"Belgin","family":"Sever","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Burdur Mehmet Akif Ersoy University, Istiklal Campus, Burdur 15200, T\u00fcrkiye"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4000","DOI":"10.2174\/0109298673267738231129104216","article-title":"Recent Advances in Signaling Pathways and Kinase Inhibitors for Leukemia Chemotherapy","volume":"32","author":"Liu","year":"2025","journal-title":"Curr. 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