2. Academic Validation
  3. Design, synthesis and biological evaluation of novel antitumor spirodihydrothiopyran-oxindole derivatives

Design, synthesis and biological evaluation of novel antitumor spirodihydrothiopyran-oxindole derivatives

  • Bioorg Med Chem Lett. 2019 Jul 1;29(13):1636-1642. doi: 10.1016/j.bmcl.2019.04.037.
Wei Liu 1,  Shuqiang Chen 2,  Fan Zhang 3,  Shipeng He 2,  Shengzheng Wang 4,  Chunquan Sheng 5
Affiliations

Affiliations

  • 1 School of Food and Biological Engineering, Shaanxi University of Science & Technology, Weiyang College Park, Xi'an 710021, People's Republic of China.
  • 2 Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China.
  • 3 Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, People's Republic of China.
  • 4 Department of Medicinal Chemistry, School of Pharmacy, Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, People's Republic of China. Electronic address: wangshengzheng001@163.com.
  • 5 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: 31047751 DOI: 10.1016/j.bmcl.2019.04.037
Abstract

Sulfur containing spiroheterocyclic oxindoles are promising privileged scaffolds in medicinal chemistry and drug discovery. Previously, we identified a new class of spirodihydrothiopyran-oxindoles with good in vitro antitumor activity against A549 lung Cancer cell line. Herein, various spirooxindole-dihydrothiopyrans with diverse substitutions were synthesized and assayed to investigate the structure-activity relationships. Among the derivatives, compounds 4b, 4i, 4m, 4n and 4q displayed superior or comparable antitumor activity than nutlin-3. Molecular mechanism study revealed this scaffold displayed moderate MDM2 inhibitory activity, significantly induced Cancer cell Apoptosis and arrested cell cycle at G0/G1 phase, which represented a good lead compound for antitumor drug discovery.

Keywords

Antitumor activity; Spirodihydrothiopyran oxindole; p53-MDM2 inhibitors.

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