New potential anticancer agents based on the anthranilic acid scaffold. Synthesis and evaluation of biological activity
New potential anticancer agents based on the anthranilic acid scaffold. Synthesis and evaluation of biological activity
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DOI：
10.1021/jm050711d
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发表时间：
2005-12-29
影响因子：
7.3
通讯作者：
Onnis, V
中科院分区：
文献类型：
--
作者：
Congiu, C;Cocco, MT;Onnis, V
报道了以邻氨基苯甲酸为骨架的新型化合物的合成及其抗癌活性。抗增殖活性由国家癌症研究所在建立的体外和体内抗癌实验模型中测定。基于氟灭酸基序的结构变化提供了一系列N-（2-（三氟甲基）-吡啶-4-基）邻氨基苯甲酸的（杂）芳基酯，其在纳摩尔至低微摩尔浓度下显示出对人肿瘤细胞系的体外生长抑制特性。吡啶基酯25在体外表现出非常有效的抗增殖功效，在整个人类肿瘤细胞系组中，化学敏感性曲线显示在低于10（-7）M的浓度下的许多GI（50）值。化合物25还在中空纤维测定和人肿瘤异种移植物中作为潜在抗癌剂进行了体内测试，显示出中等抑制性质。利用生物活性分析和比较程序来支持与抗增殖活性有关的推定生化机制。
The synthesis and anticancer activity of new compounds designed on the anthranilic acid scaffold are reported. The antiproliferative activity was assayed by the National Cancer Institute in established in vitro and in vivo anticancer experimental models. Structural variations based on the flufenamic acid motif afforded a series of (hetero)aryl esters of N-(2-(trifluoromethyl)-pyridin-4-yl)anthranilic acid, which showed in vitro growth inhibitory properties against human tumor cell lines in nanomolar to low micromolar concentrations. The pyridinyl ester 25 exhibited very potent in vitro antiproliferative efficacy, with a chemosensitive profile showing a number of GI(50) values at concentrations lower than 10(-7) M in the full panel of human tumor cell lines. Compound 25 was also tested in vivo as a potential anticancer agent in the hollow fiber assay and in human tumor xenografts, showing moderate inhibitory properties. Analysis of biological activities and the COMPARE procedure was utilized to support putative biochemical mechanisms implicated with the antiproliferative activity.