Development of actein derivatives as potent anti-triple negative breast cancer agents

Bioorg Med Chem Lett. 2023 Jun 1:89:129307. doi: 10.1016/j.bmcl.2023.129307.

Honglin Zhang ¹, Yiyan Chen ¹, Songwen Huang ¹, Wen-Wen Xiao ¹, Ming-Hua Qiu ², Li-Dong Shao ³, Chuan-Huizi Chen ⁴, Dashan Li ⁵

Affiliations

1 Yunnan Key Laboratory of Southern Medicinal Resources, School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China.
2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China. Electronic address: qiuminghua@mail.kib.ac.cn.
3 Yunnan Key Laboratory of Southern Medicinal Resources, School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China. Electronic address: shaolidong@ynutcm.edu.cn.
4 Yunnan Key Laboratory of Southern Medicinal Resources, School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China. Electronic address: huizipurple@163.com.
5 Yunnan Key Laboratory of Southern Medicinal Resources, School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China. Electronic address: lidashan@ynutcm.edu.cn.

PMID: 37121522 DOI: 10.1016/j.bmcl.2023.129307

Abstract

Actein is a natural triterpenoid glycoside, isolated from the rhizomes of Cimicifuga foetida, which have been demonstrated to be potential in the treatment of breast Cancer previously. Herein, we described the design and synthesis of a series of actein derivatives as anti-triple negative breast Cancer (TNBC) inhibitors. Of which, the most promising derivative 27 exhibited significant inhibitory activity against human TNBC cell lines HCC1806 and MDA-MB-231, with IC₅₀ values of 2.78 and 9.11 μM, respectively. Structure-activity relationships of actein derivatives were also discussed. Moreover, preliminary mechanism investigation revealed that 27 significantly inhibited Cancer cell proliferation via cell cycle arrest at S phase. In addition, western blot analysis showed that the activation of MAPK signaling pathway might contribute to derivative 27 induced cell death. Overall, these results indicate that 27 has the potential to be developed as a lead compound and compounds with the actein scaffold are a promising novel class of inhibitors to treat TNBC.

Keywords

Actein; Mechanism; Modification; Structure-activity relationships; Triple negative breast cancer.

Name
Email *

	Sorry, but the email address you supplied was invalid.