Synthesis, characterization and investigation of cholinesterase enzyme inhibition and antioxidant activities of some 4-aryl-1,4-dihydropyridine derivatives

Abstract

The aim of this study is to synthesize and characterize 4-aryl-1,4-dihydropyridine derivatives and evaluate their antioxidant and cholinesterase inhibitory properties. Hantzsch reaction was used in the synthesis of compounds; the compounds were prepared by the reaction of methyl 3-acetoacetate, appropriate aromatic aldehyde, ammonia and catalyst. The reactions were carried out in the presence of copper sulfate (for Method A) and boric acid /acetic acid catalyst (for Method B). CuSO4 was used as a catalyst for the Hantzsch reaction for the first time. The structure of the synthesized compounds were characterized by IR and1H-NMR spectral studies. Furthermore, the enzym (acetylcholinesterase and butyrylcholinesterase) inhibition activity of the synthesized compounds was evaluated using Ellman's spectrophotometrical method as a novel approach. Antioxidant studies of the synthesized compounds were performed by measuring the 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay, phosphomolibdenum-reducing antioxidant power assay, and metal chelating activity test. Results showed that 4-bromo substituted derivative (1b) has the highest antioxidant activity compared to other tested compounds. Moreover, compound 1b also has higher cholinesterase inhibitory effect (34.05 ± 2.23% and 24.93 ± 0.68% at 250 µM) than other tested compounds. In this study, eight 1,4-dihydropyridine derivatives, dimethyl 4-(phenyl/substituted phenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate compounds were synthesized according to the Hantzsch reaction, using CuSO4 as a catalyst, for the first time. Compared to the classical reaction conditions, the presence of catalyst has been offered several advantages such as excellent good yields and short reaction times.