Unlocking the Anticancer Potential of New Spirooxindoles via p53‐MDM2/MDMX Dual Inhibition: In Vitro and In Silico Assessments

= 2.03 µM). The counterparts 6b, 6k, and 6n also revealed notable inhibitory potential against p53-MDMX. The antiproliferative efficacy of the most active target compounds was assessed in HCT-116 colon cancer cell line that overexpressed MDM2 and harbored wild-type p53. The derivative 6k accomplished the highest antiproliferative activity against HCT-116 compared to nutlin-3. Moreover, 6k displayed minimal toxicity compared to the reference nutlin-3 when examined on a normal cell line. Flow cytometric analysis revealed that 6k controlled cell growth via cell cycle arrest at the G1 phase and induced cell death via apoptosis. Additionally, compound 6k revealed a prominent effect in raising p53 levels with a 6.464-fold increase compared to the control. Molecular docking and molecular dynamics simulations justified the observed efficacy. Collectively, this study showcased a new class of potent p53-MDM2/MDMX dual inhibitors possessing a spirooxindole scaffold which can be subjected to future development.