Authors
Peng Tan, Xuejiao Wei, Longyan Wang, Fei Wang, Huiming Huang, Zhuguo Wang, Xinyu Qiu, Ruoxin Zhang, Yufeng Gao, Wanying Xie, Xiaoxue Wang, Dongjun Fu, Zhongdong Hu
Published in
Bioorganic chemistry. Volume 180. Pages 110109. Jun 16, 2026. Epub Jun 16, 2026.
Abstract
Acute myelocytic leukemia (AML) is a common leukemia subtype in adults, necessitating novel, potent treatments. Microtubule-targeting agents (MTAs) are key anti-cancer drugs widely used in clinical practice. A series of novel furan-trimethoxyphenyl hybrids as tubulin polymerization inhibitors were designed using a molecular combination strategy and evaluated for their structure-activity relationships (SARs) in AML. SAR studies demonstrated that the trimethoxyphenyl unit and substituents on benzyl units play significant roles for the antiproliferative activity against human AML cells. Compound III-3 exerted the highest antiproliferative effects on human AML MV-4-11 (IC50 = 74.25 nM), HL-60 (IC50 = 87.99 nM), and THP-1 cells (IC50 = 92.20 nM). Compound III-3 could directly bind to β-tubulin at the colchicine-binding site, thereby disrupting the microtubule network structure. Compound III-3 activated the spindle assembly checkpoint (SAC), promoting M-phase arrest and mitotic catastrophe and activating the mitochondrial apoptotic pathway in AML cells. In the xenograft mouse model constructed with MV-4-11 cells, the tumor-inhibitory rate of compound III-3 (20 mg/kg body weight, 71.40%) was higher than that of the positive control Ara-C (50 mg/kg body weight, 58.41%). Thus, furan-trimethoxyphenyl hybrids are a promising class of tubulin inhibitors with potential therapeutic applications in AML.
PMID:
42320118
Bibliographic data and abstract were imported from PubMed on 20 Jun 2026.
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