Inhibition of p53-Murine Double Minute 2 (MDM2) Interactions with 3,3′-Spirocyclopentene Oxindole Derivatives

Abstract

3,3'-Spirocyclopentene oxindoles structurally related to Wang's spiropyrrolidine oxindoles have been highlighted as a new class of antiproliferative agents against cancer cell lines with wild-type p53 status (IC₅₀ up to 0.96 μM on SJSA-1 and 2.9 μM in HCT116 p53-wt). Inhibition of the MDM2-p53 interactions has been demonstrated through in vitro HTRF assays (IC₅₀ up to 3.1 nM), while Western blot analysis showed activation of p53 selectively in HCT116 cancer cell lines with wild-type p53.