{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T07:12:34Z","timestamp":1763536354981,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFD1801103"],"award-info":[{"award-number":["2022YFD1801103"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>B-cell lymphoma-2 (Bcl-2) family proteins are fundamental regulators of intrinsic cell apoptosis, and overexpression of apoptotic proteins (Bcl-2 and Mcl-1) is a characteristic of many haematological malignancies. Thus, it is necessary to discover novel inhibitors to treat leukemia. In the current study, we synthesized a series of quercetagetin derivatives (compounds 2a\u20132t, 3a\u20133j and 4a\u20134g) and evaluated their anticancer activities on four leukemia cells (U937, K562, K562R and KG-1). Among those synthesized derivatives, compounds 2a exhibited the best antiproliferative activity (IC50 = 0.276, 0.159, 0.312 and 0.271 \u00b5M to U937, K562, K562R and KG-1, respectively). In addition, 2a induced apoptosis in K562 and markedly arrested the cell cycle G2\/M phase of K562. The Western blot assay showed that 2a is a potential inhibitor that can effectively suppress the expression of Bcl-2 and Mcl-1. The molecular docking study predicted that 2a had firm interactions with the active pockets of Bcl-2 and Mcl-1. Finally, in silico pharmacokinetic evaluation of 2a indicated its potential as an anti-leukemia drug lead in the future.<\/jats:p>","DOI":"10.3390\/ijms26062727","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T07:20:00Z","timestamp":1742282400000},"page":"2727","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synthesis and Biological Evaluation of Quercetagetin Derivatives as the Inhibitors of Mcl-1 and Bcl-2 Against Leukemia"],"prefix":"10.3390","volume":"26","author":[{"given":"Kang","family":"Li","sequence":"first","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomei","family":"Ge","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Huang","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinye","family":"Lv","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhui","family":"Tang","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhehao","family":"He","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingxue","family":"Yang","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miaofen","family":"Chen","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianguo","family":"Zeng","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pi","family":"Cheng","sequence":"additional","affiliation":[{"name":"Hunan Key Laboratory of Traditional Chinese Veterinary Medicine, Hunan Agricultural University, Changsha 410128, China"},{"name":"Chinese Medicinal Materials Breeding Innovation Center of Yuelushan Laboratory, Changsha 410128, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-48445-1","article-title":"An 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