Impact of specific functional groups in flavonoids on the modulation of platelet activation

Ravishankar, D., Salamah, M., Akimbaev, A., Williams, H. F., Albadawi, D. A. I., Vaiyapuri, R., Greco, F., Osborn, H. M. I. ORCID: https://orcid.org/0000-0002-0683-0457 and Vaiyapuri, S. ORCID: https://orcid.org/0000-0002-6006-6517 (2018) Impact of specific functional groups in flavonoids on the modulation of platelet activation. Scientific Reports, 8. 9528. ISSN 2045-2322 doi: 10.1038/s41598-018-27809-z

Abstract/Summary

Flavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4th carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related peptide by optical aggregometry. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the antiplatelet activity of these flavonoids. This structure-activity relationships of flavonoids upon the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/77533
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > Mass Spectrometry (CAF) Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) > NMR (CAF) University of Reading Malaysia Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Pharmaceutics Research Group
Publisher	Nature Publishing Group
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