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

• Published in: Scientific reports Vol. 8; no. 1; pp. 9528 - 9
• Main Authors: Ravishankar, Divyashree, Salamah, Maryam, Akimbaev, Angela, Williams, Harry F., Albadawi, Dina A. I., Vaiyapuri, Rajendran, Greco, Francesca, Osborn, Helen M. I., Vaiyapuri, Sakthivel
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.06.2018; Nature Publishing Group
• Subjects: 13; 631/80; 631/92/2783; Antiplatelet therapy; Blood Platelets - drug effects; Blood Platelets - physiology; Collagen; Drug development; Flavones; Flavonoids; Flavonoids - chemistry; Flavonoids - pharmacology; Furans - chemistry; Humanities and Social Sciences; Humans; multidisciplinary; Platelet Activation - drug effects; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - chemistry; Platelet Aggregation Inhibitors - pharmacology; Platelets; Pyridines - chemistry; Science; Science (multidisciplinary); Structure-Activity Relationship; Structure-activity relationships; Sulfur; Thromboembolism; Thrombosis
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-27809-z

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 4 th 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 relationship of flavonoids with the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents.