Antiplatelet effect and selective binding to cyclooxygenase (COX) by molecular docking analysis of flavonoids and lignans

Abstract

The known flavonoids ginkgetin (1), taiwanhomoflavone A (2), taiwanhomoflavone B (3), and taiwanhomoflavone C (4) and eight known lignans: justicidin B (9), justicidin C (10), justicidin D (11), chinensinaphthol methyl ether (12), procumphthalide A (13), procumbenoside A (15), and ciliatosides A (16) and B (17) were isolated from Cephalotaxus wilsoniana and Justicia species, respectively. The antiplatelet effects of the above constituents on human platelet-rich plasma (PRP) were evaluated. Of the compounds tested on human PRP, compounds 1, 4, 9, and 11 showed inhibition of secondary aggregation induced by adrenaline. Compound 1 had an inhibitory effect on cyclooxygenase-1 (COX-1). Molecular docking studies revealed that 1 and the related compounds apigenin (5), cycloheterophyllin (6), broussoflavone F (7), and quercetin (8) were docked near the gate of active site of COX-1. It indicated that the antiplatelet effect of 1, 4, 9, and 11 is partially owed to suppression of COX-1 activity and reduced thromboxane formation. Flavonoids, 1, 5, 6, 7, and 8 may block the gate of the active site of COX-1 and interfere the conversion of arachidonic acid to prostaglandin (PG) H 2 in the COX-1 active site. © 2007 by MDPI.