Synthesis and biological evaluation of bufalin-3-yl nitrogen-containing-carbamate derivatives as anticancer agents

  • Steroids. 2016 Apr:108:56-60. doi: 10.1016/j.steroids.2016.01.011.
Min Lei  1 ,  Zhiyong Xiao  2 ,  Biao Ma  2 ,  Yijia Chen  2 ,  Miao Liu  2 ,  Junhua Liu  3 ,  De'an Guo  2 ,  Xuan Liu  4 ,  Lihong Hu  5
Affiliations
  • 1. Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: [email protected].
  • 2. Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
  • 3. Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
  • 4. Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: [email protected].
  • 5. Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: [email protected].
PMID: 26827628 DOI: 10.1016/j.steroids.2016.01.011
Abstract

A series of bufalin-3-yl nitrogen-containing-carbamate derivatives 3 were designed, synthesized, and evaluated for their proliferation inhibition activities against human cervical epithelial adenocarcinoma (HeLa) cell line. The structure-activity relationships (SARs) of this new series are described in this paper. Cytotoxicity data revealed that the C3 moiety had an important influence on cytotoxic activity. Compound 3i-HCl exhibited significant in vitro antiproliferative activity against the ten tested tumor cell lines, with IC50 values ranging from 0.30 to 1.09 nM. Furthermore, 3i-HCl can significantly inhibit tumor growth by 100% at the dose 2 mg/kg by iv, or 4 mg/kg by ig.

Keywords
Bufalin (BF); Bufalin-3-yl carbamate; Cardiac glycosides; Cytotoxicity; Natural product.
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