期刊
TETRAHEDRON
卷 74, 期 39, 页码 5585-5614出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tet.2018.07.028
关键词
Natural products; Salinomycin; Molecular editing; Coordination chemistry; Cancer; Cancer stem cells; Iron; Fenton chemistry; Medicinal chemistry; Chemical biology
资金
- European Research Council [647973]
- Emergence Ville de Paris
- Ligue Contre le Cancer
- PSL University
Cancer stem cells (CSC) have been shown to be refractory to conventional therapeutic agents, can promote metastasis, and have been linked to cancer relapse. The natural product Salinomycin has been identified by means of high throughput phenotypic screening as a selective killer of CSC in vitro and in vivo. In this article we comprehensively review the chemistry of Salinomycin, documenting early total syntheses, along with strategies that have been developed over the years to effectively modify this natural product at key positions with the view to establish a robust structure-activity-relationship and to delineate the complex mechanism of action of this fascinating molecule in the context of cancer research. Then, we document the biology of Salinomycin, putting forward phenotypic alterations that have been observed in the relevant biological models and highlighting how chemistry has been instrumental in discovering unprecedented physiological features of cancer stem cells that can be exploited for therapeutic benefits. (C) 2018 Elsevier Ltd. All rights reserved.
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