Li L, Wang H K, Kuo S C, Wu T S, Mauger A, Lin C M, Hamel E, Lee K H
Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill 27599.
J Med Chem. 1994 Sep 30;37(20):3400-7. doi: 10.1021/jm00046a025.
A series of 3',6,7-substituted 2-phenyl-4-quinolones were designed and synthesized as antimitotic antitumor agents. All compounds showed cytotoxic effects (log GI50 < or = -4.0; log drug molar concentration required to cause 50% inhibition) against the growth of a variety of human tumor cell lines, including those derived from solid tumors such as non-small cell lung, colon, central nervous system, ovary, prostate, and breast cancers, when evaluated in the National Cancer Institute's 60 human tumor cell line in vitro screen. The most potent compound (26) demonstrated strong cytotoxic effects with GI50 values in the nanomolar or subnanomolar range in almost all the tumor cell lines. Compound 26 was also a potent inhibitor of tubulin polymerization and radiolabeled colchicine binding to tubulin, with activity comparable to those of the potent antimitotic natural products colchicine, podophyllotoxin, and combretastatin A-4.
设计并合成了一系列3'，6，7-取代的2-苯基-4-喹诺酮类化合物作为抗有丝分裂抗肿瘤药物。在国立癌症研究所的60种人类肿瘤细胞系体外筛选中评估时，所有化合物对多种人类肿瘤细胞系的生长均显示出细胞毒性作用（log GI50≤ -4.0；导致50%抑制所需的药物摩尔浓度对数），包括那些源自实体瘤的细胞系，如非小细胞肺癌、结肠癌、中枢神经系统癌、卵巢癌、前列腺癌和乳腺癌。最具活性的化合物（26）在几乎所有肿瘤细胞系中均表现出强烈的细胞毒性作用，其GI50值在纳摩尔或亚纳摩尔范围内。化合物26也是微管蛋白聚合和放射性标记秋水仙碱与微管蛋白结合的有效抑制剂，其活性与强效抗有丝分裂天然产物秋水仙碱、鬼臼毒素和康普瑞他汀A-4相当。
