2. Academic Validation
  3. Design, synthesis, and anti-triple negative breast cancer activity of novel Toosendanin derivatives

Design, synthesis, and anti-triple negative breast cancer activity of novel Toosendanin derivatives

  • Bioorg Med Chem Lett. 2023 Mar 1:83:129187. doi: 10.1016/j.bmcl.2023.129187.
Honglin Zhang 1,  Yiyan Chen 1,  Qiuyu Liu 1,  Wen-Wen Xiao 1,  Li-Dong Shao 2,  Zheng-Hong Pan 3,  Chuan-Huizi Chen 4,  Dashan Li 5
Affiliations

Affiliations

  • 1 Yunnan Key Laboratory of Southern Medicinal Resources, School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China.
  • 2 Yunnan Key Laboratory of Southern Medicinal Resources, School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China. Electronic address: [email protected].
  • 3 Guangxi Key Laboratory of Functional Phytochemicals Research and Utilization, Guangxi Institute of Botany, Guangxi Zhuang Autonomous Region and Chinese Academy of Sciences, Guilin 541006, China. Electronic address: [email protected].
  • 4 Yunnan Key Laboratory of Southern Medicinal Resources, School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China. Electronic address: [email protected].
  • 5 Yunnan Key Laboratory of Southern Medicinal Resources, School of Chinese Materia Medica, Yunnan University of Chinese Medicine, Kunming 650500, China. Electronic address: [email protected].
PMID: 36781147 DOI: 10.1016/j.bmcl.2023.129187
Abstract

Toosendanin (TSN) is a natural anti-cancer compound that is isolated from the traditional Chinese herbal Melia toosendan Sieb et Zucc. However, the research effect of TSN in the treatment of Triple negative breast Cancer (TNBC) is still far from ideal. In this work, we investigated TSN and its derivatives in terms of their actions against MDA-MB-231 and HCC1806 TNBC cell lines. The results indicated that TSN and its derivative 11 showed excellent antitumor activity. Preliminary mechanistic studies showed that both compounds TSN and 11 induced S-phase arrest and G2/M phase cell number decrease in HCC1806 cells. Also, TSN and 11 significantly reduced the protein level of the well-known Cancer suppressor gene p53, reduced the phosphorylation of Akt and ERK, and also induced the accumulation of phosphorylated p38 and p21.

Keywords

Mechanism; Structure-activity relationships; Toosendanin; Triple negative breast cancer.

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