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Molecules 2018, 23(10), 2612; https://doi.org/10.3390/molecules23102612

Enzyme-Site Blocking Combined with Optimization of Molecular Docking for Efficient Discovery of Potential Tyrosinase Specific Inhibitors from Puerariae lobatae Radix

1,2,†
,
1,†
,
1
,
1,* and 3,*
1
Jiangsu key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
2
School of Science, China Pharmaceutical University, Nanjing 211198, China
3
School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 1 August 2018 / Revised: 3 October 2018 / Accepted: 7 October 2018 / Published: 11 October 2018
(This article belongs to the Section Natural Products Chemistry)
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Abstract

Enzyme inhibitors from natural products are becoming an attractive target for drug discovery and development; however, separating enzyme inhibitors from natural-product extracts is highly complex. In this study, we developed a strategy based on tyrosinase-site blocking ultrafiltration integrated with HPLC-QTOF-MS/MS and optimized molecular docking to screen tyrosinase inhibitors from Puerariae lobatae Radix extract. Under optimized ultrafiltration parameters, we previously used kojic acid, a known tyrosinase inhibitor, to block the tyrosinase active site in order to eliminate false-positive results. Using this strategy, puerarin, mirificin, daidzin and genistinc were successfully identified as potential ligands, and after systematic evaluation by several docking programs, the rank of the identified compounds predicted by computational docking was puerarin > mirificin > kojic acid > daidzin ≈ genistin, which agreed with the results of tyrosinase-inhibition assays. Structure-activity relationships indicated that C-glycosides showed better tyrosinase inhibition as compared with O-glycosides, with reduced inhibition achieved through the addition of glycosyl, which provides ideas about the screen of leading compounds and structural modification. View Full-Text
Keywords: affinity-ultrafiltration-MS; molecular docking; tyrosinase inhibitors affinity-ultrafiltration-MS; molecular docking; tyrosinase inhibitors
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Liu, H.; Zhu, Y.; Wang, T.; Qi, J.; Liu, X. Enzyme-Site Blocking Combined with Optimization of Molecular Docking for Efficient Discovery of Potential Tyrosinase Specific Inhibitors from Puerariae lobatae Radix. Molecules 2018, 23, 2612.

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