The synthesis and biologic evaluation of anti-platelet and cytotoxic β-nitrostyrenes

Our previous studies demonstrated that two cytotoxic beta-nitrostyrene derivatives, 3,4-methylenedioxy-beta-nitrostyrene (MNS) and 4-O-benzoyl-3-methoxy-beta-nitrostyrene (BMNS) exhibit potent anti-platelet activities. In this study, a series of beta-nitrostyrenes were synthesized and subjected to anti-platelet aggregation assay and cytotoxicity assay. The mono-and di-substitutions on the B ring of BMNS tended to increase the anti-platelet activity and decrease the cytotoxic activity. Of these, compounds 19 and 24 exhibited the most potent inhibitory effects on thrombin-and collagen-induced platelet aggregation (IC(50) <= 0.7 mu M) without significant cytotoxicity on a human cancer cell line (up to 20 mu M). Further studies indicated that compounds 19 and 24 inhibited platelet aggregation via prevention of glycoprotein IIb/IIIa activation. The potent and novel effects of BMNS derivatives make them attractive candidates for the development of new anti-platelet agents. (C) 2010 Elsevier Ltd. All rights reserved.