This hybrid structure aimed to combine MDM2 inhibition, which promotes p53-mediated apoptosis in wild-type p53 cancers, with the BCL2-modulatory properties of marinopyrrole A. Among the synthesized compounds, 5i and 5q emerged as the most promising, exhibiting potent pro-apoptotic activity with IC50 values below 1μM in MDA-MB, HepG2, and Caco-2 cancer cell lines, adequate solubility, and minimal toxicity to healthy cells. This evidence concerns the gene MDM2 and cancer.