微管菌素类似物的合成及抗肿瘤活性

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, ¹³C 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.

Synthesis and Anti-tumor Activity of Tubulysins Analogues†

Tubulysins family is a kind of natural compound with potent antitumor activity. To simplify the synthesis 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 conformation 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).