新型汉防己甲素衍生物的合成及其生物活性

Synthesis of Novel Tetrandrine Derivatives and Their Biological Activities

以汉防己甲素为原料,经溴代反应制得关键中间体5-溴汉防己甲素(2);2与硼酸衍生物经Suzuki反应合成了6个新型的汉防己甲素衍生物(4a^4f),其结构经1H NMR,13C NMR和ESI-MS表征。采用CCK-8法初步考察了4a^4f对人早幼粒白血病细胞(HL60)和人肺癌细胞(A549)的抑制活性;并采用MTT法对活性较好的化合物进行复筛。采用酶联免疫吸附法考察4a^4f对多种受体酪氨酸激酶的抑制活性。结果表明:4b,4c和4e对HL60和A549有一定的抑制活性;4b和4c对受体酪氨酸激酶FGFR1的抑制活性大于50%。

Six novel tetrandrine derivatives（ 4a - 4f） were synthesized by Suzuki coupling reaction of boronic acid derivatives and 5-bromotetrandrine,which was obtained by bromination,using tetrandrine as the starting material. The structures were characterized by1 H NMR,13 C NMR and ESI-MS. The inhibition activities of 4a - 4f against A549 and HL60 cancer cell lines were investigated by CCK-8 assay. The compounds which had better inhibition activities were secondary screened by MTT assay. The inhibitory activities of 4a - 4f against PTKs were tested by ELISA. The results showed that 4b,4c and4 e exhibited well inhibition activities against the two cancer cell lines. 4b and 4c showed better inhibition activities against FGFR1.