Functional and binding studies of gallic acid showing platelet aggregation inhibitory effect as a thrombin inhibitor
This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine (TCM) and evaluating its biological activity in vitro and binding characteristics. A combination strategy containing molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and m...
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Published in | Chinese herbal medicines Vol. 14; no. 2; pp. 303 - 309 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Singapore
Elsevier B.V
01.04.2022
Elsevier |
Subjects | |
Online Access | Get full text |
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Summary: | This study was devoted to identifying natural thrombin inhibitors from traditional Chinese medicine (TCM) and evaluating its biological activity in vitro and binding characteristics.
A combination strategy containing molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation were applied to verify the study result.
Gallic acid was confirmed as a direct thrombin inhibitor with IC50 of 9.07 μmol/L and showed a significant inhibitory effect on thrombin induced platelet aggregation. SPR-based binding studies demonstrated that gallic acid interacted with thrombin with a KD value of 8.29 μmol/L. Molecular dynamics and binding free energy analysis revealed that thrombin-gallic acid system attained equilibrium rapidly with very low fluctuations, the calculated binding free energies was −14.61 kcal/mol. Ala230, Glu232, Ser235, Gly258 and Gly260 were the main amino acid residues responsible for thrombin inhibition by gallic acid, providing a mechanistic basis for further optimization.
This study proved that gallic acid is a direct thrombin inhibitor with platelet aggregation inhibitory effect, which could provide a basis for the follow-up research and development for novel thrombin inhibitors. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1674-6384 2589-3610 2589-3610 |
DOI: | 10.1016/j.chmed.2021.09.001 |