New Schiff Base–TMB Hybrids: Design, Synthesis and Antiproliferative Investigation as Potential Anticancer Agents

Abstract

The structural symmetry or asymmetry of organic compounds is one of the most fundamental characteristics. Z-geometrical isomers are promiscuous and kinetically preferred structures with a plethora of biological activities. A new series of hybrid molecules containing Schiff base and 3,4,5-trimethoxybenzamide moieties were synthesized from the starting material ethyl acrylate ester derivative (Z)-1 and structurally confirmed by elemental microanalysis, 1H-NMR, and 13C-NMR spectroscopic studies. The in vitro cytotoxic activity of the target hybrids was tested against the MCF-7 breast cancer line compared with colchicine as the reference compound. Most of the newly synthesized hybrids showed good growth inhibition activity against the MCF-7 cells compared to the reference substance. The results of the β-tubulin polymerization inhibition activity assay showed that the p-vanillin Schiff base 4g displayed good inhibition activity. In addition, p-vanillin Schiff base 4g exhibited antiproliferative activity over the MCF-7 cells by cellular cycle blockade at the G2/M phase and it is a potent apoptotic agent. qRT-PCR analysis showed that Schiff base 4g boosted the mRNA expression of the p53 and Bax levels while lowering the expression of the Bcl-2 level.

Keywords

• Schiff base
• trimethoxybenzamide
• cytotoxicity
• tubulin
• cell cycle analysis
• mRNA expression