三阴性乳腺癌
紫杉醇
化学
乳腺癌
癌症研究
天然产物
转移
癌症
药理学
立体化学
医学
内科学
作者
Hong Yao,Shaowen Xie,Xiaoqian Ma,Junkai Liu,Hongyu Wu,Aijun Lin,Hequan Yao,Dahong Li,Shengtao Xu,Dong‐Hua Yang,Zhe‐Sheng Chen,Jinyi Xu
标识
DOI:10.1021/acs.jmedchem.0c00408
摘要
Triple-negative breast cancer (TNBC) is one of the most highly invasive and metastatic breast cancers without safe and effective therapeutic drugs. The natural product oridonin is reported to be a potential anti-TNBC agent. However, its moderate activity and complex structure hampered its clinical application. In this study, the novel oridonin analogues were first identified by removal of multiple hydroxyl groups and structural simplification of oridonin. The representative analogue 20 exhibited potent anticancer effects. Further structural modification on 20 generated the most potent derivative 56, which possessed 120-fold more potent antiproliferative activity than oridonin in the TNBC cell line HCC1806. Importantly, compound 56 exhibited more potent anticancer activity than paclitaxel in TNBC xenograft nude mice. Moreover, 56 could attenuate the expression of MMP-2, MMP-9, p-FAK, and integrin β1 to inhibit TNBC cell metastasis. All results suggest that compound 56 may warrant further investigation as a promising candidate agent for the treatment of TNBC.
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