| Summary: | Abstract Background 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 recent years. Results Starting from 3-nitrobenzoic acid, after 7 steps transformations, 12 new tubulysin analogues were synthesized by the conformational restraint and bioisostere principle. These structures are featuring 3-substituted analine moieties. All these compounds are new compounds, and the structures were characterized by 1H NMR, 13C NMR, and HRMS. The antitumor activities were screened by the MTT method using MDA-MB-231and MCF7 cells. Conclusions Compound IIb exhibited certain antitumor activity with the IC50 value of 7.6 and 11.8 µM against MDA-MB-231 and MCF7 cells respectively. Compounds IIa–IIe had moderate antitumor activities suggested that the thiazole ring in the Tuv could be replaced by the phenyl ring. However, Compounds Ia–Ie lose antitumor activity dramatically suggested that the conformation of the Tuv was crucial for the tubulysin analogues to maintain the biological activity.
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