INTRODUCTION AND OBJECTIVES: p53 is a phosphoprotein composed of 53 kDa and 393 amino acids; it is encoded by the TP53 gene that is located on the short arm of chromosome 17. When active, p53 adopts a tetrameric form and is mostly regulated by the MDM2 protein. Known as a “guardian of the human genome”, p53, under stress conditions, is able to promote the cell cycle stop in the G1/S phase, the induction of p21, among other defense mechanisms, allowing the repair of DNA that was previously disabled. If these mechanisms fail, p53 protein triggers the apoptotic cascade signals and the cells can go to into apoptosis, preventing the error from spreading. There are few studies regarding the role of vitamin K in the activation of wild-type p53, however, there is evidence that vitamin K2 is capable of inducing apoptosis via p53 in hepatocarcinoma cell lines that express wild-type p53 (Smmc-7721). Bearing in mind that vitamin K2 induces apoptosis by activating wild-type p53, we aim to test a group of compounds, which are menadione derivatives with methyl-1,2,3-triazole substitutions in breast cancer cell lines that express wild type p53. MATERIAL AND METHODS: To clarify the mechanism of p53 activation in breast cancer cell lines expressing wild-type p53, we screened the vitamin K-derived compounds by evaluating cell viability using the MTT reduction technique in MCF-7 (wild-type p53) and MDA-MB-231 (mutant p53). In addition, the dose-response curve (IC50) of selected compounds was performed after the cell viability assay. RESULTS AND CONCLUSION: With screening assay, using the compounds at 10 µM, we observed that, after 72 h, six compounds (RCT-02, RCT-04, RCT-07, RCT-11 and RCT-12) were more effective to decrease the cellular viability of MCF-7 cells when compared to MDA-MB-231 cells. The compounds that decreased MCF-7 cell viability by 50% or more, when compared to the same treatment in the mutant cell line were chosen to continue this study. Subsequently, with dose-response curves, we were able to calculate the IC50 values of these compounds. Given the above findings, we will seek in the future to assess which of the six compounds are capable of activating and modulating wild-type p53, as well as to elucidate the molecular components involved in the process.