Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis
| العنوان: | Discovery of a New Class of Cathepsin K Inhibitors in Rhizoma Drynariae as Potential Candidates for the Treatment of Osteoporosis |
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| المؤلفون: | Xinluan Wang, Zuo Cheng Qiu, Ka Chun Wong, Xin Sheng Yao, Man Sau Wong, Gao Keng Xiao, Yi Dai, Xiao-Li Dong |
| المصدر: | International Journal of Molecular Sciences, Vol 17, Iss 12, p 2116 (2016) International Journal of Molecular Sciences; Volume 17; Issue 12; Pages: 2116 International Journal of Molecular Sciences |
| بيانات النشر: | MDPI AG, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Osteoporosis, Cathepsin K, Pharmacology, Kushennol F, Sophoraflavanone G, lcsh:Chemistry, Mice, chemistry.chemical_compound, RAW264.7 cells, 0302 clinical medicine, Osteogenesis, lcsh:QH301-705.5, Spectroscopy, biology, Drug discovery, in silico target fishing, General Medicine, osteoporosis, Rhizoma Drynariae, osteoclasts, bone resorption, Computer Science Applications, Molecular Docking Simulation, RANKL, 030220 oncology & carcinogenesis, Flavanones, Proteases, In silico, Article, Catalysis, Bone resorption, Cell Line, Inorganic Chemistry, 03 medical and health sciences, Polypodiaceae, medicine, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, business.industry, RANK Ligand, Organic Chemistry, medicine.disease, RAW 264.7 Cells, 030104 developmental biology, chemistry, lcsh:Biology (General), lcsh:QD1-999, biology.protein, Plant Preparations, business |
| الوصف: | Rhizoma Drynariae (RD), as one of the most common clinically used folk medicines, has been reported to exert potent anti-osteoporotic activity. The bioactive ingredients and mechanisms that account for its bone protective effects are under active investigation. Here we adopt a novel in silico target fishing method to reveal the target profile of RD. Cathepsin K (Ctsk) is one of the cysteine proteases that is over-expressed in osteoclasts and accounts for the increase in bone resorption in metabolic bone disorders such as postmenopausal osteoporosis. It has been the focus of target based drug discovery in recent years. We have identified two components in RD, Kushennol F and Sophoraflavanone G, that can potentially interact with Ctsk. Biological studies were performed to verify the effects of these compounds on Ctsk and its related bone resorption process, which include the use of in vitro fluorescence-based Ctsk enzyme assay, bone resorption pit formation assay, as well as Receptor Activator of Nuclear factor κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis using murine RAW264.7 cells. Finally, the binding mode and stability of these two compounds that interact with Ctsk were determined by molecular docking and dynamics methods. The results showed that the in silico target fishing method could successfully identify two components from RD that show inhibitory effects on the bone resorption process related to protease Ctsk. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::82da41ee6acf8b5167aebf109f8077b3 http://www.mdpi.com/1422-0067/17/12/2116 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....82da41ee6acf8b5167aebf109f8077b3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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