The synthesis and biologic evaluation of anti-platelet and cytotoxic β-nitrostyrenes.
Our previous studies demonstrated that two cytotoxic β-nitrostyrene derivatives, 3,4-methylenedioxy-β-nitrostyrene (MNS) and 4-O-benzoyl-3-methoxy-β-nitrostyrene (BMNS) exhibit potent anti-platelet activities. In this study, a series of β-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 μM) without significant cytotoxicity on a human cancer cell line (up to 20 μM). 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.
Hsieh
Pei-Wen
PW
Graduate Institute of Natural Products, Chang Gung University, Taoyuan 333, Taiwan. pewehs@mail.cgu.edu.tw
Chang
Yu-Ting
YT
Chuang
Wen Yin
WY
Shih
Hsin-Chu
HC
Chiang
Shin-Zan
SZ
Wu
Chin-Chung
CC
D045744:Cell Line, Tumor; D006801:Humans; D039661:Integrin beta3 / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
D039661:Integrin beta3; D010975:Platelet Aggregation Inhibitors; D013343:Styrenes; C011955:beta-nitrostyrene