2. Academic Validation
  3. Synthesis and biological evaluation of salinomycin triazole analogues as anticancer agents

Synthesis and biological evaluation of salinomycin triazole analogues as anticancer agents

  • Eur J Med Chem. 2017 Feb 15:127:900-908. doi: 10.1016/j.ejmech.2016.10.067.
Minjian Huang 1,  Zixin Deng 2,  Jian Tian 3,  Tiangang Liu 4
Affiliations

Affiliations

  • 1 Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan, 430071, China.
  • 2 Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan, 430071, China; Hubei Engineering Laboratory for Synthetic Microbiology, Wuhan Institute of Biotechnology, Wuhan, 430075, China.
  • 3 Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan, 430071, China; Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, China. Electronic address: Jian.Tian@whu.edu.cn.
  • 4 Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan, 430071, China; Hubei Engineering Laboratory for Synthetic Microbiology, Wuhan Institute of Biotechnology, Wuhan, 430075, China. Electronic address: liutg@whu.edu.cn.
PMID: 27876192 DOI: 10.1016/j.ejmech.2016.10.067
Abstract

Salinomycin, a polyether Antibiotic used for treatment of coccidial disease in Animal Husbandry, has demonstrated promising efficacy for treating different cancers. To enrich structure-activity relationship of salinomycin in tumours, we prepared a series of new triazole derivatives in specific site of salinomycin by click cycloaddition reactions, and assessed their antiproliferative activities on breast Cancer cell lines. The screening results indicated that most derivatives modified at the C20 hydroxyl group have potent antitumour activity. Notably, salinomycin triazole dimers were 3.27-4.97 times more toxic than the natural substance in ERα-positive breast Cancer cells (MCF-7), and had moderately improved toxicity in triple-negative breast Cancer cells (MDA-MB-231).

Keywords

Anticancer activity; Breast cancer; CuAAC reaction; Salinomycin.

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