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
