2. Academic Validation
  3. Design, synthesis and biological evaluation of novel antitumor spirotetrahydrothiopyran-oxindole derivatives as potent p53-MDM2 inhibitors

Design, synthesis and biological evaluation of novel antitumor spirotetrahydrothiopyran-oxindole derivatives as potent p53-MDM2 inhibitors

  • Bioorg Med Chem. 2017 Oct 15;25(20):5268-5277. doi: 10.1016/j.bmc.2017.07.049.
Changjin Ji 1,  Shengzheng Wang 2,  Shuqiang Chen 3,  Shipeng He 4,  Yan Jiang 3,  Zhenyuan Miao 3,  Jian Li 5,  Chunquan Sheng 6
Affiliations

Affiliations

  • 1 School of Pharmacy, East China University of Science & Technology, 130 Meilong Road, Shanghai 200237, People's Republic of China; Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, People's Republic of China.
  • 3 Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
  • 4 School of Pharmacy, East China University of Science & Technology, 130 Meilong Road, Shanghai 200237, People's Republic of China.
  • 5 School of Pharmacy, East China University of Science & Technology, 130 Meilong Road, Shanghai 200237, People's Republic of China. Electronic address: jianli@ecust.edu.cn.
  • 6 Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: shengcq@smmu.edu.cn.
PMID: 28797774 DOI: 10.1016/j.bmc.2017.07.049
Abstract

p53-MDM2 protein-protein interaction is a promising target for novel antitumor drug development. Previously, we identified a new class of spirotetrahydrothiopyran-oxindole p53-MDM2 inhibitors by novel organocatalytic enantioselective cascade reactions. Herein, a series of new derivatives were designed, synthesized and assayed to investigate the structure-activity relationships. Among them, compound B14 bearing a novel spiroindole-thiopyranopyridone scaffold exhibited potent MDM2 inhibitory activity as well as antitumor activity, which could effectively induce the Apoptosis of A549 Cancer cells. It represents a promising lead compound for the development of novel antitumor agents.

Keywords

Antitumor activity; Organocatalytic cascade reaction; Spirooxindole; p53–MDM2 inhibitors.

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