Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis
Abstract
:1. Introduction
2. Results
2.1. In Silico Target Fishing
2.2. Kushennol F (KF) and Sophoraflavone G (SG) Directly Inhibited the Proteolytic Activity of Cathepsin K
2.3. Kushennol F and Sophoraflavone G Suppressed RANKL-induced Osteoclastogenesis of RAW264.7
2.4. Kushennol F and Sophoraflavone G Significantly Inhibited Bone Resorption Pit Formation
2.5. Molecular Docking Analysis
2.6. Molecular Dynamic(MD) Simulations
3. Discussion
4. Materials and Methods
4.1. The Establishment of RD Ingredients Database
4.2. In Silico Target Fishing
4.3. Experimental Validation
4.3.1. Chemicals and Reagents
4.3.2. Cathepsin K Inhibition Activity Assay
4.3.3. RAW264.7 Cell Culture
4.3.4. Cell Cytotoxicity Assay
4.3.5. TRAP Positive Multinucleated Cells Staining
4.3.6. TRAP Activity Measurement
4.3.7. Pit Formation Assay
4.4. Docking Analysis
4.5. Molecular Dynamics
4.6. Statistical Analysis
5. Conclusions
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
Abbreviations
Ctsk | Cathepsin K |
RD | Rhizoma Drynariae |
KF | Kushennol F |
SG | Sophoraflavanone G |
TCM | Traditional Chinese Medicine |
MNCs | Multi-nucleated cells |
TRAP | Tartrate-resistant acid phosphatase |
MD | Molecular Dynamics |
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Parameters | Compound Identifier | |
---|---|---|
Kushennol F | Sophoraflavanone G | |
ANN | PRD | -- |
pIC50 | 6.8 | -- |
REF_NN | FVNFXIPJDHVJGE-REZTVBANSA-N | -- |
SIM | 0.841 | 0.838 |
REF_pACT | 6.77 | -- |
SOURCE_DB | ChemblDB, PubChem, Binding DB | -- |
UNIPROT | P43235 | -- |
TARGET NAME | Cathepsin K | -- |
FUNCTIONAL | EC, FD, PS | -- |
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Qiu, Z.-C.; Dong, X.-L.; Dai, Y.; Xiao, G.-K.; Wang, X.-L.; Wong, K.-C.; Wong, M.-S.; Yao, X.-S. Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis. Int. J. Mol. Sci. 2016, 17, 2116. https://doi.org/10.3390/ijms17122116
Qiu Z-C, Dong X-L, Dai Y, Xiao G-K, Wang X-L, Wong K-C, Wong M-S, Yao X-S. Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis. International Journal of Molecular Sciences. 2016; 17(12):2116. https://doi.org/10.3390/ijms17122116
Chicago/Turabian StyleQiu, Zuo-Cheng, Xiao-Li Dong, Yi Dai, Gao-Keng Xiao, Xin-Luan Wang, Ka-Chun Wong, Man-Sau Wong, and Xin-Sheng Yao. 2016. "Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis" International Journal of Molecular Sciences 17, no. 12: 2116. https://doi.org/10.3390/ijms17122116