2. Academic Validation
  3. Design and synthesis of conformationally constrained salinomycin derivatives

Design and synthesis of conformationally constrained salinomycin derivatives

  • Eur J Med Chem. 2017 Sep 29:138:353-356. doi: 10.1016/j.ejmech.2017.06.063.
Wenxuan Zhang 1,  Jun Wu 2,  Bo Li 3,  Xu Lian 3,  Jie Xia 3,  Qi Zhou 2,  Song Wu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: wxzhang@imm.ac.cn.
  • 2 State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
  • 3 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 4 State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: ws@imm.ac.cn.
PMID: 28688275 DOI: 10.1016/j.ejmech.2017.06.063
Abstract

Two conformationally restricted salinomycin derivatives by tethering the hydroxyl groups at C1 and C20 with different chain length were designed and synthesized. The cyclic derivatives showed better biological activities than C1/C20 modified derivatives, indicating the importance of the compact conformation for the ion binding capacity. In addition, the length of the connective chain plays critical role in the biological activities, thus cyclic the derivative 7 preserved some pharmacological activity but derivative 5 with two carbon atom shorter chain showed significantly reduced activity. The conformations of the two cyclic salinomycin derivatives were analyzed by ROESY spectrum in DMSO-d6, indicating derivative 7 may adopt more appropriate conformations for the coordinate with alkali metal ion than derivative 5, which has a closer distance between H3 and H25.

Keywords

Anti-cancer; Conformational restriction; Salinomycin.

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