2. Academic Validation
  3. Design and synthesis of novel hydroxyanthraquinone nitrogen mustard derivatives as potential anticancer agents via a bioisostere approach

Design and synthesis of novel hydroxyanthraquinone nitrogen mustard derivatives as potential anticancer agents via a bioisostere approach

  • Eur J Med Chem. 2015 Sep 18:102:303-9. doi: 10.1016/j.ejmech.2015.08.006.
Li-Ming Zhao 1,  Feng-Yan Ma 2,  Hai-Shan Jin 2,  Shilong Zheng 3,  Qiu Zhong 3,  Guangdi Wang 4
Affiliations

Affiliations

  • 1 School of Chemistry and Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China. Electronic address: lmzhao@jsnu.edu.cn.
  • 2 School of Chemistry and Chemical Engineering, and Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China.
  • 3 RCMI Cancer Research Center and Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA.
  • 4 RCMI Cancer Research Center and Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA. Electronic address: gwang@xula.edu.
PMID: 26291039 DOI: 10.1016/j.ejmech.2015.08.006
Abstract

A series of hydroxyanthraquinones having an alkylating N-mustard pharmacophore at 1'-position were synthesized via a bioisostere approach to evaluate their cytotoxicity against four tumor cell lines (MDA-MB-231, HeLa, MCF-7 and A549). These compounds displayed significant in vitro cytotoxicity against MDA-MB-231 and MCF-7 cells, reflecting the excellent selectivity for the human breast Cancer. Among them, compound 5k was the most cytotoxic with IC50 value of 0.263 nM and is more potent than DXR (IC50 = 0.294 nM) in inhibiting the growth of MCF-7 cells. The excellent cytotoxicity and good selectivity of compound 5k suggest that it could be a promising lead for further design and development of Anticancer agents, especially for breast Cancer.

Keywords

Anthraquinone; Antitumor activity; Nitrogen mustard; Synthesis.

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