Novel quinolin-4-ylcarbonylhydrazine having N-(3-arylacryloyl) moiety: Design, synthesis and biological evaluation as potential cytotoxic agents against MDA-MB-231 via tubulin assembly inhibition

•A new set of quinolin-4-ylcarbonylhydrazine derivatives having 2-arylamido-3-arylacryloyl moiety has been synthesized.•The newly synthesized derivatives were evaluated for their cytotoxic activity against MDA-MB-231 cancer cells.•Flow cytometric measurements were carried out for the most potent molecule.•Active compound was tested for β-tubulin assembly inhibition.•Mitochondrial membrane potential was assessed for the most active compound. A new set of quinolin-4-ylcarbonylhydrazine derivatives 7a-i and 9a,b bearing 3-arylacryloyl moiety has been synthesized and investigated for their potential anticancer activity. The synthetic protocol involves the following step: the target quinoline derivatives 7a-i and 9a,b appended to the acryloyl moiety were synthesized from quinolin-4-carbohydrazide intermediate with respective ethyl 2-arylamido-3-arylacrylate compounds. The cytotoxic activity study was evaluated using the functional MTT method. The most of target compounds displayed potent cytotoxic activity against MDA-MB-231 cell line. Among them, compounds 7d and 7 h were found to be promising antiproliferative agents with IC50 values of 4.04 and 1.78 μM, respectively, relative to the effective anticancer drug, Dox (IC50 = 5.33 μM). Compound 7 h exhibited cytotoxic activity by causing cell cycle to block at G2/M phase in addition to pro-apoptotic effect, as shown by flow cytometric measurement. In addition, the inhibitory action against β-tubulin polymerization was investigated. Finally, compound 7 h diminished the level of mitochondrial potential by almost 2.8-fold compared to control, indicating that the cellular death proceeds through the provoke of the intrinsic mitochondrial pathway of apoptosis.