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 H-1 nuclear magnetic resonance (NMR), C-13 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 II b exhibited moderate antitumor activity(7.6 and 11.8 mu mol/ L).