New inhibitors of matrix metalloproteinases 9 (MMP-9): Lignans from Selaginella moellendorffii

被引:15
|
作者
Zhu, Yuan [1 ]
Huang, Ri-Zhen [2 ,3 ]
Wang, Chun-Gu [1 ]
Ouyang, Xi-Lin [1 ]
Jing, Xiao-Teng [1 ]
Liang, Dong [1 ]
Wang, Heng-Shan [1 ]
机构
[1] Guangxi Normal Univ, Sch Chem & Pharmaceut Sci, State Key Lab Chem & Mol Engn Med Resources, 15 Yucai Rd, Guilin 541004, Guangxi, Peoples R China
[2] Southeast Univ, Pharmaceut Res Ctr, Nanjing, Jiangsu, Peoples R China
[3] Southeast Univ, Sch Chem & Chem Engn, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Lignans; Selaginella moellendorffii; Matrix metalloproteinase; Migration; Anticancer activity; CANCER PROGRESSION; NEOLIGNANS; INVASION; HIERON; CELLS; METASTASIS; MIGRATION; INSIGHTS;
D O I
10.1016/j.fitote.2018.09.008
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Matrix metalloproteinase 9 (MMP-9) is one of the structurally related zinc-dependent endopeptidases families and provides a new target for cancer therapy owing to its pivotal role in metastatic tumors. In this paper, fourteen lignans, including three novel lignans, named selamoellenin B-D (1-3), and eleven known lignan derivatives (4-14) were isolated from the plant of Selaginella moellendorffii. Among them, compound 3 is optically active, which was enantiomerically seperated to afford a pair of enantiomers, ( - )-3 and ( + )-3. Their structures were elucidated by extensive spectroscopic analyses. Their cytotoxic activities were evaluated against four human cancer cell lines. Among them, five compounds (4, 5, 6, 11 and 13) exhibited great potent cytotoxicity and their structure-activity relationships were also discussed. All compounds except for 3 lignan analogues with low cytotoxicity were selected for further in vitro enzyme inhibition, surface plasmon resonance (SPR), and molecular docking assays based on the MMPs target. The results shown that, compound 11 have the best inhibitory effect and can be considered as a potential drug candidate targeting at MMP-9 for cancer therapy.
引用
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页码:281 / 289
页数:9
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