Congiu Cenzo, Cocco Maria Teresa, Lilliu Valentina, Onnis Valentina
Dipartimento di Tossicologia, Università di Cagliari, Via Ospedale 72, Cagliari, I-09124, Italy.
J Med Chem. 2005 Dec 29;48(26):8245-52. doi: 10.1021/jm050711d.
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.
报道了基于邻氨基苯甲酸支架设计的新化合物的合成及其抗癌活性。美国国立癌症研究所采用既定的体外和体内抗癌实验模型测定了其抗增殖活性。基于氟芬那酸基序的结构变化得到了一系列N-(2-(三氟甲基)吡啶-4-基)邻氨基苯甲酸的(杂)芳基酯，这些酯在纳摩尔至低微摩尔浓度下对人肿瘤细胞系表现出体外生长抑制特性。吡啶基酯25表现出非常强的体外抗增殖功效，其化学敏感性曲线显示在整个人类肿瘤细胞系中，在浓度低于10(-7) M时具有多个GI(50)值。化合物25还作为潜在的抗癌剂在中空纤维试验和人肿瘤异种移植模型中进行了体内测试，显示出中等抑制特性。利用生物活性分析和COMPARE程序来支持与抗增殖活性相关的假定生化机制。
