四氢异喹啉类衍生物设计、合成及p21活化激酶4抑制活性与研究.pdfVIP

四氢异喹啉类衍生物的设计、合成及p21 活化激酶 4 抑制活性研究 1 1 2 2* 1* 1 宋帅，高禄华，郭冰玉，李丰 ，赵冬梅 ，程卯生 (1. 沈阳药科大学 基于靶点的药物设计与研究教育部重点实验室，辽宁，沈阳 110016; 2. 中国医科大学，辽宁，沈阳 110001) 摘要：目的：研究四氢异喹啉类化合物的抗肿瘤构效关系，寻找具有抗肿瘤活性的新型四氢异喹啉类化合物。 方法：以那可丁为先导化合物，合成系列化合物。采用MTT实验、激酶发光实验、流式细胞术、蛋白质印 迹法、细胞体外侵袭实验对合成的目标化合物进行了初步作用机制研究。结果：合成了8个目标化合物，经 1H-NMR 和 MS 确证其结构。药理实验表明，所合成的化合物具有一定的p21活化激酶4抑制活性。结论： 此类结构具有较好的p21活化激酶4抑制活性，值得进一步研究。 关键词：四氢异喹啉；p21活化激酶4 ；抑制剂；抗肿瘤 Design, synthesis and inhibit activities of p21-activated kinase 4 of tetrahydroisoquinoline derivatives 1 1 2 2* 1* SONG Shuai , GAO Luhua , GUO Bing-yu , LI Feng , ZHAO Dong-mei ,CHENG 1 Maosheng (1 ．Key Laboratory of Structure-Based Drug Design Discovery, Ministry of Education Shenyang Pharmaceutical University, Shenyang 110016, China; 2.China Medical University，Shenyang 110001, China) ABSTRACT: OBJECTIVE To study the structure-activity relationship (SAR) of tetrahydroisoquinoline derivatives and search for novel anticancer agents. METHODS A series of tetrahydroisoquinoline derivatives were synthesized based on the lead command Noscapine. Their inhibit activities of p21-activated kinase 4 were evaluated by MTT assay, FCM assay, Kinase Glo, Western Blot, Transwell assay, respectively. RESULTS August new compounds were synthesized and confirmed by 1H-NMR and MS. Some of the target compounds showed inhibit activities of p21-activated kinase 4. CONCLUSION Tetrahydroisoquinoline derivatives, which shows desirable inhibit activities of p21-activated kinase 4 and analgesic activity c