Poplawski J, Lozowicka B, Dubis A T, Lachowska B, Witkowski S, Siluk D, Petrusewicz J, Kaliszan R, Cybulski J, Strzałkowska M, Chilmonczyk Z
Institute of Chemistry, University of Bialystok, J. Pilsudskiego 11/4, 15-443 Bialystok, Poland.
J Med Chem. 2000 Oct 5;43(20):3671-6. doi: 10.1021/jm000905n.
A series of alpha-asarone isomers was synthesized and investigated for their hypolipidemic and antiplatelet activity. Considering the hypolipidemic activity in rats at a dose of 80 mg/kg/day, some isomers were more potent than clofibrate at 150 mg/kg. Compound 3 was one of the most active agents elevating the HDL cholesterol level by 56% and lowering the LDL cholesterol level by 46.8% in rats after 7 days of administration. The activities of the platelet aggregation test in vitro were significant but lower than those of the reference substances (indomethacine and acetylsalicylic acid). In the pulmonary thromboembolic in vivo test in mice, two compounds (alpha-asarone (6) and compound 4) produced significant antithrombotic effects at 100 mg/kg, namely 44% and 52% protection against lung microembolia, respectively. alpha-Asarone derivatives form a new group of potential hypolipidemic and/or antithrombotic agents. The compounds 3, 4, and 6 may serve as lead substances whose structural modifications may result in original drugs.
合成了一系列α-细辛脑异构体，并对其降血脂和抗血小板活性进行了研究。考虑到在大鼠中剂量为80mg/kg/天时的降血脂活性，一些异构体比氯贝丁酯在150mg/kg时更有效。化合物3是最具活性的药物之一，给药7天后，大鼠的高密度脂蛋白胆固醇水平升高56%，低密度脂蛋白胆固醇水平降低46.8%。体外血小板聚集试验的活性显著，但低于参考物质（吲哚美辛和乙酰水杨酸）。在小鼠体内肺血栓栓塞试验中，两种化合物（α-细辛脑（6）和化合物4）在100mg/kg时产生了显著的抗血栓作用，分别对肺微栓塞有44%和52%的保护作用。α-细辛脑衍生物形成了一类新的潜在降血脂和/或抗血栓药物。化合物3、4和6可作为先导物质，其结构修饰可能产生原创药物。
