New inhibitors of matrix metalloproteinases 9 (MMP-9): Lignans from Selaginella moellendorffii
| Autor: | Dong Liang, Heng-Shan Wang, Xi-Lin Ouyang, Jing Xiaoteng, Yuan Zhu, Chun-Gu Wang, Ri-Zhen Huang |
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| Rok vydání: | 2018 |
| Předmět: |
Selaginellaceae
China Phytochemicals Matrix metalloproteinase Matrix Metalloproteinase Inhibitors 01 natural sciences Lignans chemistry.chemical_compound Structure-Activity Relationship Selaginella moellendorffii Cell Line Tumor Drug Discovery Cytotoxic T cell Humans Cytotoxicity Pharmacology Lignan biology Molecular Structure 010405 organic chemistry Chemistry General Medicine biology.organism_classification Antineoplastic Agents Phytogenic In vitro 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Biochemistry Matrix Metalloproteinase 9 Cell culture Enantiomer |
| Zdroj: | Fitoterapia. 130 |
| ISSN: | 1873-6971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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