Park Byeoung-Soo, Son Dong-Ju, Choi Won-Sik, Takeoka Gary R, Han Sung Ok, Kim Tae-Wan, Lee Sung-Eun
Institute of Ecological Phytochemistry, Hankyong National University, Ansung-City, Kyonggi-Do 456-749, Korea.
Phytother Res. 2008 Sep;22(9):1195-9. doi: 10.1002/ptr.2432.
Piperlongumine, a pyridone alkaloid isolated from Piper longum L., exhibited a potential inhibitory effect on washed rabbit platelet aggregation induced by collagen, arachidonic acid (AA) and platelet activating factor (PAF), without any inhibitory effect on that induced by thrombin. Piperlongumine was used as a lead compound for the synthesis of new antiplatelet agents. Seven synthetic compounds were newly synthesized from 3,4,5-trimethoxycinnamic acid (TMCA). They were 1-piperidin-1-yl-3-(3,4,5-trimethoxy-phenyl)prop-2-en-1-one (1'), 1-morpholin-4-yl-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (2'), 1-(3,5-dimethylpiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (3'), 1-(2-methylpiperidin-1-yl)-3-(3,4,5-tri-methoxyphenyl)prop-2-en-1-one (4'), 1-(3-hydroxypiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)- prop-2-en-1-one (5'), 1-[3-(3,4,5-tri-methoxyphenyl) acryloyl]-piperidin-2-one (6') and ethyl 1-[3-(3,4,5-trimethoxyphenyl)-acryloyl]piperidine-4-carboxylate (7'). Among those seven synthetic derivatives, 1-(3,5-dimethylpiperidin-1-yl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (3') had the most inhibitory effect on platelet aggregation induced by collagen, AA and PAF.
荜茇酰胺是从荜茇中分离得到的一种吡啶酮生物碱，对胶原、花生四烯酸（AA）和血小板活化因子（PAF）诱导的兔洗涤血小板聚集具有潜在抑制作用，而对凝血酶诱导的血小板聚集没有任何抑制作用。荜茇酰胺被用作合成新型抗血小板药物的先导化合物。从3,4,5-三甲氧基肉桂酸（TMCA）新合成了7种化合物。它们分别是1-哌啶-1-基-3-(3,4,5-三甲氧基苯基)丙-2-烯-1-酮（1'）、1-吗啉-4-基-3-(3,4,5-三甲氧基苯基)丙-2-烯-1-酮（2'）、1-(3,5-二甲基哌啶-1-基)-3-(3,4,5-三甲氧基苯基)丙-2-烯-1-酮（3'）、1-(2-甲基哌啶-1-基)-3-(3,4,5-三甲氧基苯基)丙-2-烯-1-酮（4'）、1-(3-羟基哌啶-1-基)-3-(3,4,5-三甲氧基苯基)丙-2-烯-1-酮（5'）、1-[3-(3,4,5-三甲氧基苯基)丙烯酰基]-哌啶-2-酮（6'）和1-[3-(3,4,5-三甲氧基苯基)丙烯酰基]哌啶-4-羧酸乙酯（7'）。在这7种合成衍生物中，1-(3,5-二甲基哌啶-1-基)-3-(3,4,5-三甲氧基苯基)丙-2-烯-1-酮（3'）对胶原、AA和PAF诱导的血小板聚集具有最强的抑制作用。
