微管菌素类似物的合成及抗肿瘤活性

Synthesis and Anti-tumor Activity of Tubulysins Analogues

以微管菌素为先导化合物,设计合成了一系列类似物;所有化合物的结构均经~1H NMR,^(13)C NMR及HRMS确证,均为新化合物.采用噻唑蓝(MTT)法对其抗肿瘤活性进行了初步筛选,结果表明,化合物Ⅱb具有一定的抗肿瘤活性.

Tubulysins family is a kind of natural compound with potent antitumor activity. To simplify the syn- thesis route and find new antitumor compounds is becoming a hotspot of research in recent years. Starting from 3-nitrobenzoic acid, after 7 steps transformations, 12 new tubulysin analogues were synthesized via the confor- mation restrain and bioisostere principle. These structures are featuring 3-substituted analine moieties. All these compounds are new compounds, and their structures were confirmed by 1H nuclear magnetic resonance （NMR）, 13C NMR, and high resolution mass spectrometer（HRMS）. The antitumor activities were tested by the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyetl trazolium bromide （MTT） method in vitro using MDA-MB- 231 and MCF7 cells, and compound Ⅱb exhibited moderate antitumor activity（7.6 and 11.8 μmol/L）.