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This study shows the design, synthesis and antitumoral potential evaluation of a novel chalcone-like compound, ( E )-3- (3, 5-di- ter- butyl-4-hydroxyphenyl)-1- (4-hydroxy-3-methoxyphenyl) prop-2-en-1-one [LQFM064) ( 4 )], against human breast adenocarcinoma MCF7 cells. Some toxicological parameters were also investigated. LQFM064) ( 4 ) exhibited cytotoxic activity against MCF7 cells (IC 50 = 21 μM), in a concentration dependent-manner, and triggered significant changes in cell morphology and biochemical/molecular parameters, which are suggestive of an apoptosis inductor. LQFM064) ( 4 ) (21 μM) induced cell cycle arrest at G0/G1 phase with increased p53 and p21 expressions. It was also shown that the compound ( 4 ) did not interfere directly in p53/MDM2 complexation of MCF7 cells. In these cells, externalization of phosphatidylserine, cytochrome c release, increased expression of caspases-7, − 8 and − 9, reduced mitochondrial membrane potential and ROS overgeneration were also detected following LQFM064 ( 4 ) treatment. Further analysis revealed the activation of both apoptotic pathways via modulation of the proteins involved in the extrinsic and intrinsic pathways with an increase in TNF-R1, Fas-L and Bax levels and a reduction in Bcl-2 expression. Furthermore, KIT proto-oncogene receptor tyrosine kinase, insulin-like growth factor (IGF1) and platelet-derived growth factor receptor A (PDGFRA) were downregulated, while glutathione S-transferase P1 (GSTP1) and interferon regulatory factor 5 (IRF5) expressions were increased by LQFM064 ( 4 )-triggered cytotoxic effects in MCF7 cells. Moreover, it can be inferred that compound ( 4 ) has a moderate acute oral systemic toxicity hazard, since its estimated LD 50 was 452.50 mg/kg, which classifies it as UN GHS Category 4 (300 mg/kg > LD 50 < 2000 mg/kg). Furthermore, LQFM064 ( 4 ) showed a reduced potential myelotoxicity (IC 50 = 150 μM for mouse bone marrow hematopoietic progenitors). In conclusion, LQFM064 ( 4 ) was capable of inducing breast cancer cells death via different cytotoxic pathways. Thus, it is a promising alternative for the treatment of neoplasias, especially in terms of the drug resistance development. [ABSTRACT FROM AUTHOR]