2. Academic Validation
  3. Synthesis and biological evaluation of novel steroidal 5α,8α-epidioxyandrost-6-ene-3β-ol-17-(O-phenylacetamide)oxime derivatives as potential anticancer agents

Synthesis and biological evaluation of novel steroidal 5α,8α-epidioxyandrost-6-ene-3β-ol-17-(O-phenylacetamide)oxime derivatives as potential anticancer agents

  • Bioorg Med Chem Lett. 2017 Aug 15;27(16):3856-3861. doi: 10.1016/j.bmcl.2017.06.048.
Ming Bu 1,  Tingting Cao 2,  Hongxia Li 2,  Mingzhou Guo 3,  Burton B Yang 4,  Chengchu Zeng 2,  Yue Zhou 2,  Na Zhang 2,  Liming Hu 5
Affiliations

Affiliations

  • 1 Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China; College of Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.
  • 2 Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China.
  • 3 Chinese PLA General Hospital, Beijing 100853, China.
  • 4 Sunnybrook Research Institute, University of Toronto, Toronto M4N3M5, Canada.
  • 5 Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China; Beijing Key Laboratory of Environmental and Viral Oncology, Beijing University of Technology, Beijing 100124, China. Electronic address: huliming@bjut.edu.cn.
PMID: 28666736 DOI: 10.1016/j.bmcl.2017.06.048
Abstract

Inspired by the significant anti-cancer activity of our previously screened natural ergosterol peroxide (EP, 1), we synthesized and characterized a series of novel 5α,8α-epidioxyandrost-3β-ol-17-(O-phenylacetamide)oxime derivatives (9a-o). The anti-proliferative activity of the synthesized compounds against human hepatocellular carcinoma cells (HepG2, Sk-Hep1) and human breast Cancer cells (MCF-7, MDA-MB231) were investigated. Compounds 9d, 9f, 9h, 9j and 9m displayed good anti-proliferative activity (most IC50<20μM) in vitro. Furthermore, fluorescence imaging showed that the designed coumarin-9d conjugate (12) localized mainly in mitochondria, leading to enhanced Anticancer activities over the parent structure.

Keywords

Cytotoxic activities; Endoperoxide; Ergosterol peroxide; Photooxygenation; Steroidal derivatives.

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