Synthesis and antitumor activities of 3-substituted-analine derivatives: structure modifications of Tuv part of tubulysins.

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.

SUBMITTER: Shao M 

PROVIDER: S-EPMC6768038 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature