2. Academic Validation
  3. Novel racemosin B derivatives as new therapeutic agents for aggressive breast cancer

Novel racemosin B derivatives as new therapeutic agents for aggressive breast cancer

  • Bioorg Med Chem. 2018 Dec 15;26(23-24):6096-6104. doi: 10.1016/j.bmc.2018.11.014.
Xiao Xiao 1,  Mei Xu 2,  Chao Yang 2,  Yao Yao 2,  Li-Na Liang 2,  Philip Ed Chung 3,  Qun Long 4,  Eldad Zacksenhaus 3,  Zhixu He 5,  Sheng Liu 6,  Yaacov Ben-David 7
Affiliations

Affiliations

  • 1 State Key Laboratory for Functions and Applications of Medicinal Plants/College of Basic Medical Sciences, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR China; Stem Cell and Tissue Engineering Research Center, Laboratory Animal Center, Department of Immunology, Guizhou Medical University, Guiyang 550004, PR China.
  • 2 State Key Laboratory for Functions and Applications of Medicinal Plants/College of Basic Medical Sciences, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR China.
  • 3 Department of Medicine, University of Toronto, Toronto, Ontario M5G2M1, Canada; Division of Advanced Diagnostics, Toronto General Research Institute-University Health Network, Toronto, Ontario M5G2M1, Canada.
  • 4 State Key Laboratory for Functions and Applications of Medicinal Plants/College of Basic Medical Sciences, Guizhou Medical University, Guiyang 550014, PR China; Stem Cell and Tissue Engineering Research Center, Laboratory Animal Center, Department of Immunology, Guizhou Medical University, Guiyang 550004, PR China.
  • 5 State Key Laboratory for Functions and Applications of Medicinal Plants/College of Basic Medical Sciences, Guizhou Medical University, Guiyang 550014, PR China; Stem Cell and Tissue Engineering Research Center, Laboratory Animal Center, Department of Immunology, Guizhou Medical University, Guiyang 550004, PR China. Electronic address: hzx@gmc.edu.cn.
  • 6 State Key Laboratory for Functions and Applications of Medicinal Plants/College of Basic Medical Sciences, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR China. Electronic address: lsheng@126.com.
  • 7 State Key Laboratory for Functions and Applications of Medicinal Plants/College of Basic Medical Sciences, Guizhou Medical University, Guiyang 550014, PR China; The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang 550014, PR China. Electronic address: yaacovbendavid@hotmail.com.
PMID: 30471828 DOI: 10.1016/j.bmc.2018.11.014
Abstract

Carbazole derivatives show anti-cancer activity and are of great interest for drug development. In this study, we synthesized and analyzed several new alkylamide derivatives of racemocin B, a natural indolo[3,2-a]carbazole molecule originally isolated from the green alga Caulerpa racemose. Several alkylamide derivatives were found to exhibit moderate to strong growth inhibition against human breast Cancer cell lines. They induced G2/M cell cycle arrest and Apoptosis in the aggressive triple-negative breast Cancer cell line MDA-MB-231. Among these derivatives, compound 25 with the lowest IC50 induced cell death by suppressing Autophagy. This was accompanied by inhibition of autophagic flux and accumulation of Autophagy protein 1 light chain 3, LC3II, and p62. The novel alkylamide derivative offers a potential new treatment for human breast Cancer.

Keywords

Apoptosis; Autophagy; Breast cancer; Carbazole; Racemocin B.

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