Synthesis and biological relationships of 3′,6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives as antimitotic agents
Synthesis and biological relationships of 3′,6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives as antimitotic agents
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DOI：
10.1016/j.bmc.2004.09.041
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发表时间：
2005-01-03
影响因子：
3.5
通讯作者：
Kuo, SC
中科院分区：
文献类型：
--
作者：
Lai, YY;Huang, LJ;Kuo, SC
作为在2-苯基-4-喹诺酮系列中持续寻找潜在的抗癌药物候选物的一部分，合成并评价了3 ′，6-取代的2-苯基-4-喹诺酮-3-羧酸衍生物及其盐。初步筛选表明，含有间氟取代的2-苯基的羧酸类似物显示出最高的体外抗癌活性。如果氯或甲氧基取代氟原子，活性显著降低。在所有测试的羧酸衍生物及其盐中，3 '-氟-6-甲氧基-2-苯基-4-喹诺酮-3-羧酸（68）具有最高的体外细胞毒性活性。作用机制可能与微管蛋白结合药物（如诺维本和紫杉醇）相似，但不完全相同。化合物68作为一种新的亲水性抗有丝分裂剂值得进一步研究。(C)2004爱思唯尔有限公司保留所有权利。
As part of a continuing search for potential anticancer drug candidates in the 2-phenyl-4-quinolone series, 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives and their salts were synthesized and evaluated. Preliminary screening showed that carboxylic acid analogs containing a m-fluoro substituted 2-phenyl group displayed the highest in vitro anticancer activity. Activity decreased significantly if a chlorine or methoxy group replaced the fluorine atom. 3'-Fluoro-6-methoxy-2-phenyl-4-quinolone-3-carboxylic acid (68) had the highest in vitro cytotoxic activity among all tested carboxylic acid derivatives and their salts. The mechanism of action may be similar, but not identical, to that of tubulin binding drugs, such as navelbine and taxol. Compound 68 merits further investigation as a novel hydrophilic antimitotic agent. (C) 2004 Elsevier Ltd. All rights reserved.