Synthesis and Biological Evaluation of Quercetagetin Derivatives as the Inhibitors of Mcl-1 and Bcl-2 Against Leukemia
Year: 2025
Type: article
Abstract: 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–2t, 3a–3j and 4a–4g) 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 µM 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.
DOI: 10.3390/ijms26062727
Authors: Kang Li, Xiaomei Ge, Wei Liu, Lei Huang, Xinye Lv, Yuhui Tang, Zhehao He, Yingxue Yang, Miaofen Chen, Jianguo Zeng, Pi Cheng
Institution: Hunan Agricultural University
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
Award: G2121690079
OpenAlex ID: W4408549468