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The diarylpentanoids with the best docking scores obeying the druglikeness and ADMET prediction properties were subsequently synthesized and evaluated for their antiproliferative activity on colon cancer HCT116 and fibroblasts HFF\u20101 cells. The effect on p53\u2010MDM2\/X interactions was evaluated through yeast\u2010based assays for compounds showing potent antiproliferative activity in HCT116 cells and low toxicity in normal cells, resulting in the identification of a potential dual inhibitor. Moreover, its antiproliferative effect was significantly reduced in the absence of p53 and in MDA\u2010MB\u2010231 cells expressing a mutant p53 form. The antiproliferative effect of this compound was associated with induction of cell cycle arrest, apoptosis, PARP cleavage and increased p53 and its transcriptional targets, p21 and PUMA, in HCT116 cells. Docking poses and residues involved in the inhibition of p53\u2010MDM2\/X interactions were predicted by docking studies.<\/jats:p>","DOI":"10.1002\/cmdc.202100337","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T06:16:15Z","timestamp":1624601775000},"page":"2969-2981","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A Diarylpentanoid with Potential Activation of the p53 Pathway: Combination of <i>in silico<\/i> Screening Studies, Synthesis, and Biological Activity Evaluation"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9883-8412","authenticated-orcid":false,"given":"Joana","family":"Moreira","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Qu\u00edmica Org\u00e2nica e Farmac\u00eautica Departamento de Ci\u00eancias Qu\u00edmicas Faculdade de Farm\u00e1cia Universidade do Porto  Rua de Jorge Viterbo Ferreira, 228 4050-313 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