以重组人DNA拓扑异构酶Ⅰ为靶位从天然产物及其衍生物中筛选抗肿瘤化合物

Screening of Antitumor Compounds from Natural Compounds or Its Derivatives by Using the Recombinant Human DNA Topoisomerase Ⅰ as Target

为了在体外以人DNA拓扑异构酶Ⅰ(hTopoⅠ)为靶位进行抗肿瘤化合物的快速筛选,首次使用毕赤酵母表达了hTopoⅠ。在微量反应体系中,测定了化合物抑制hTopoⅠ松驰活性的能力,并用MTT实验验证筛选到的hTopoⅠ抑制剂的抗肿瘤活性。从74个结构新颖的天然产物及人工合成的黄酮类衍生物中筛到6个hTopoⅠ抑制剂,有4个化合物抑制肿瘤细胞生长的能力较强。

In order to rapidly screen new antitumor compounds targeting at human DNA topoisomerase Ⅰ (hTopoⅠ), hTopoⅠ was first expressed by \$P. pastoris\$ and used in the screening. In a total 20μL hTopoⅠ reaction system, the abilities of compounds to inhibit the relaxing activity of hTopoⅠ were detected and their IC50 were determined. The antitumor activities of these hTopoⅠ inhibitors were tested by MTT method. Six hTopoⅠ inhibitors were found from 74 natural compounds and flavone derivatives, and four hTopoⅠ inhibitors showed strong antitumor activity.