Wang Tai-Chi, Chen I-Li, Lu Chai-Ming, Kuo Daih-Huang, Liao Chang-Hui
Department of Pharmacy, Tajen Institute of Technology, Pingtung 907, Taiwan, Republic of China.
Chem Biodivers. 2005 Feb;2(2):253-63. doi: 10.1002/cbdv.200590008.
A series of oxime- and methyloxime-containing flavone, isoflavone, and xanthone derivatives (1-12) were synthesized (Scheme) and evaluated for their cytotoxic (Table 1) and antiplatelet activities (Table 2). The in vitro anticancer assay indicated that the cytotoxicity of structurally related compounds decreases in the order isoflavones (7a-7c) > flavones (8a-8c) > xanthones (9a-9c), electron-releasing substituents (R) on the Ph ring being favorable (mean GI50 values of 2.84, 12.3, and 20.9 microM for 7c, 8c, and 9c, resp.). The inhibition of platelet aggregation induced by arachidonic acid (AA) similarly decreased from the isoflavone 1 (IC50 = 2.97 microM) to the flavone 2 (7.70 microM) to the xanthone 3 (inactive). Thereby, compound 1 seems to be a promising lead, since it was not only the most-potent aggregation inhibitor (IC50 = 2.97 microM), but was also found to be noncytotoxic at a concentration of 100 microM.
合成了一系列含肟和甲基肟的黄酮、异黄酮和呫吨酮衍生物（1 - 12）（见方案），并对其细胞毒性（表1）和抗血小板活性（表2）进行了评估。体外抗癌试验表明，结构相关化合物的细胞毒性按以下顺序降低：异黄酮（7a - 7c）>黄酮（8a - 8c）>呫吨酮（9a - 9c），苯环上的供电子取代基（R）较为有利（7c、8c和9c的平均GI50值分别为2.84、12.3和20.9 microM）。花生四烯酸（AA）诱导的血小板聚集抑制作用同样从异黄酮1（IC50 = 2.97 microM）降低到黄酮2（7.70 microM）再到呫吨酮3（无活性）。因此，化合物1似乎是一个有前景的先导化合物，因为它不仅是最有效的聚集抑制剂（IC50 = 2.97 microM），而且在浓度为100 microM时还被发现无细胞毒性。
