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.
- 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: [email protected].
- 5. Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, People's Republic of China. Electronic address: [email protected].
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.