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

• Published in: BMC chemistry 2018-11, Vol.12 (1), p.115-8, Article 115
• Main Authors: Shao, Mingsha, Bai, Xinfa, Ma, Xuan, Yan, Ning, Yao, Lei
• Format: Article
• Language: English
• Subjects: Analogues; Anticancer properties; Antitumor activity; Biological activity; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Nitrobenzoic acid; NMR; Nuclear magnetic resonance; Organic and Medicinal Chemistry; Research Article; Substitutes; Synthesis; Tubulysin
• ISSN: 1752-153X; 1752-153X; 2661-801X
• DOI: 10.1186/s13065-018-0483-5

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 1 H NMR, 13 C 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 IC 50 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.