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

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.