Design, synthesis and protein-binding character of an acylhydrazone anticancer candidate.

• An acylhydrazone compound was designed as an anticancer candidate. • Nitryl (–NO 2) and methyl (–CH 3) were introduced to adjust the hydrophobicity. • MNB-BSA binding was an endothermal spontaneous process driven by entropy. • MNB had appropriate albumin affinity and acceptable blood toxicity. Acylhydrazone derivatives have potential antitumor activities due to their metabolic modulation effect in cancer cells. Herein, an acylhydrazone compound, p -nitrobenzaldehyde- p -methylbenzoylhydrazone (MNB), was designed, prepared and characterized. The interaction of MNB with carrier protein is systematically deciphered using spectroscopic, electrochemical and modeling techniques. Ultraviolet (UV) and electrochemical impedance spectroscopy (EIS) indicate that MNB can couple with albumin through hydrophobic interaction. Molecular probe experiments reveal MNB is located at Sudlow's site I in albumin. Stern-Volmer equation, Langmuir adsorption isotherm, van't Hoff equation and Arrhenius equation are applied to analyze the thermodynamic and kinetic characteristics of the interaction. The results demonstrate that the interaction is a typical spontaneous process dominated by entropy, whose activation energy is ca. 26.78 kJ·mol−1. Circular dichroism (CD) spectra show that MNB has a small impact on the conformation of albumin. Molecular docking investigation simulates the structural details of the new complex, which is consistent with experimental conclusions. This study provides comprehensive information on the interaction of MNB with carrier protein, which lays the basis for its application as a new anticancer candidate. [ABSTRACT FROM AUTHOR]