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Open AccessArticle

Discovery of a Natural Syk Inhibitor from Chinese Medicine through a Docking-Based Virtual Screening and Biological Assay Study

by Xing Wang 1,2, Junfang Guo 1, Zhongqi Ning 1 and Xia Wu 1,2,*
1
School of Traditional Chinese Medicine, Capital Medical University, Fengtai District, Beijing 100069, China
2
Beijing Key Lab of Traditional Chinese Medicine Collateral Disease Theory Research, Capital Medical University, Fengtai District, Beijing 100069, China
*
Author to whom correspondence should be addressed.
Academic Editors: Rino Ragno and Milan Mladenović
Molecules 2018, 23(12), 3114; https://doi.org/10.3390/molecules23123114
Received: 5 November 2018 / Revised: 20 November 2018 / Accepted: 26 November 2018 / Published: 28 November 2018
(This article belongs to the Special Issue Application of Computational Methods in Drug Design)
Spleen tyrosine kinase (Syk) is a critical target protein for treating immunoreceptor signalling-mediated allergies. In this study, a virtual screening of an in-house Chinese medicine database followed by biological assays was carried out to identify novel Syk inhibitors. A molecular docking method was employed to screen for compounds with potential Syk inhibitory activity. Then, an in vitro kinase inhibition assay was performed to verify the Syk inhibitory activity of the virtual screening hits. Subsequently, a β-hexosaminidase release assay was conducted to evaluate the anti-mast cell degranulation activity of the active compounds. Finally, tanshinone I was confirmed as a Syk inhibitor (IC50 = 1.64 μM) and exhibited anti-mast cell degranulation activity in vitro (IC50 = 2.76 μM). Docking studies showed that Pro455, Gln462, Leu377, and Lys458 were key amino acid residues for Syk inhibitory activity. This study demonstrated that tanshinone I is a Syk inhibitor with mast cell degranulation inhibitory activity. Tanshinone I may be a potential lead compound for developing effective and safe Syk-inhibiting drugs. View Full-Text
Keywords: Syk inhibitors; tanshinone I; virtual screening; Syk inhibition assay; cell-based assay Syk inhibitors; tanshinone I; virtual screening; Syk inhibition assay; cell-based assay
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MDPI and ACS Style

Wang, X.; Guo, J.; Ning, Z.; Wu, X. Discovery of a Natural Syk Inhibitor from Chinese Medicine through a Docking-Based Virtual Screening and Biological Assay Study. Molecules 2018, 23, 3114.

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