Synthesis, characterization and biological research of novel 2-(quinoline-4-carbonyl)hydrazide-acrylamide hybrids as potential anticancer agents on MCF-7 breast carcinoma cells by targeting EGFR-TK

Abstract

Novel derivatives of the 2-(quinoline-4-carbonyl)hydrazide scaffold carrying the acrylamide moiety were synthesized and tested for their cytotoxic efficacy against the breast carcinoma MCF-7 cell line. The most active members 6a, 6b and 6h revealed significant antiproliferative action with an IC₅₀ value of 3.39, 5.94 and 2.71 μM, respectively, which were more potent than the reference drug Dox (IC₅₀ = 6.18 μM). Aiming to enlighten the antiproliferative activity, compounds 6a and 6h were examined for their inhibitory potential against EGFR kinase. The results demonstrated that compound 6h displayed potent inhibitory activity, as concluded from the IC₅₀ value (IC₅₀ = 0.22 μM) compared to the standard drug Lapatinib (IC₅₀ value of 0.18 μM). Compound 6h was found to induce significant cellular cycle arrest at the G1 phase and provoke apoptosis. Besides, compound 6h triggered apoptosis <i>via</i> upregulating p53 and initiator caspase 9 by 7.4- and 8.7-fold, respectively, compared to DMSO controls.