Solvent-Free Mechanochemical Synthesis, Characterization, and Enzyme Inhibitory Evaluation of Novel Chalcone Derivatives

Abstract

This type of compound with α,β-unsaturated ketone structure has an extensive structural diversity and broad bioactivity, and is an important class of compound in drug discovery, such as chalcones [2]. This study reports on the synthesis of eight new chalcone derivatives (NC-1 through NC-8), which were obtained via a solvent-free mechanochemical Claisen–Schmidt condensation method in keeping with principles of green chemistry. Under seal condition, the synthesis was performed via mechanical oxidation of acetophenones with various substituents and aromatic aldehydes in solid state with potassium hydroxide as base catalyst. It has removed the cumbersome factor of organic solvents, minimized the time for the reaction and provided the desired products in considerable yields.
The chalcone derivatives synthesized appeared as crystalline solids which isolated on workup and characterized on the basis of percentage yield, TLC behavior, and melting point determination for purity and structural integrity. As shown, the yields were moderate to high, illustrating the efficiency of the mechanochemical method. The effect of ABA and ABA derivatives via aromatic substitution on coupled physicochemical properties was revealed through changes in Rf values and melting points.
Chalcones were synthesized and evaluated their inhibitory activity against two enzymes, α-amylase and trypsin, by in-vitro enzymatic studies. All of the compounds were inhibitory to some measurable degree, and the differences were ascribed to   electronic and steric effects of the substituents on the aromatic rings. That is to say that the presence of electron-withdrawing and halogen substituents in the chalcones generally produced stronger inhibition on the enzymes. These results demonstrate the potential of this pathway-mediated strategy to be employed for mechanochemically synthesized scaffolds to for enzyme inhibition and medicinal chemistry direction.