基于均相时间分辨荧光高通量筛选模型的脱氢枞胺衍生物酪氨酸激酶抑制活性研究

蛋白酪氨酸激酶已成为引人注目、治疗多种疾病的新靶点。本研究建立了基于均相时间分辨荧光技术的高通量筛选模型，用于筛选脱氢枞胺系列衍生物的酪氨酸激酶抑制活性。构效关系分析发现具有氮侧链的脱氢枞胺衍生物有较好的酪氨酸激酶抑制活性，有卤素取代苯环基的脱氢枞胺衍生物具有较好的表皮生长因子受体抑制活性。该研究结果显示：脱氢枞胺衍生物经结构改造有望开发成为一类新型、多靶点、高效的蛋白酪氨酸激酶抑制剂。

Tyrosine kinase inhibitory activity of dehydroabietylamine de- rivatives tested by homogeneous time-resolved fluorescence based high throughput screening model

Protein tyrosine kinases （PTKs） are attractive targets in searching for therapeutic agents against many diseases. In this study, a series of dehydroabietylamine derivatives were first determined to show PTK inhibitory activity using a high-throughput screening （HTS） method based on homogeneous time-resolved fluorescence （HTRF） technology. The structure-activity relationships of the dehydroabietylamine derivatives were established, and it was found that the compounds with a nitrogen-containing side chain had better inhibitory activity. Further studies showed that the compounds substituted with halogen in the phenyl ring resulted in higher inhibitory activity on the epidermal growth factor receptor （EGFR）, and can be a guide to modify the structure of dehydroabietylamine derivatives. Dehydroabietylamine derivatives might be a new class of multi-targeted and effective PTK inhibitors with structure modi- fications.