Discovery of N-pyridazin-3-piperidine derivatives acting as p53 activators against breast cancer: In vitro and in silico evaluations

Abstract

Transcription factor p53 plays an important role in tumor suppression, including apoptosis and cell cycle arrest. Inhibition of murine double minute 2 (MDM2)-p53 interaction with small molecules has been shown to reactivate p53 and inhibit tumor growth. In this investigation, we developed an innovative series of N-pyridazin-3-piperidine derivatives as potential p53 activators against breast cancer. Among these, compound D16 emerged as a highly effective p53 activator, demonstrating strong efficacy against the MCF-7 cell line while maintaining minimal toxicity toward normal human cells. This article demonstrates an efficient protocol to design and synthesize potent biologically active compounds, providing a basis for developing novel p53 activators.