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 and 1 H-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, phosphomolibdenumreducing 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-3,5dicarboxylate 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.

Bio-Catalysis in Multicomponent Reactions

“…The Hantzsch reaction, first reported in 1882, is a well-known protocol for the synthesis of 1,4-dihydropyridines (DHPs) from ethyl acetoacetate, an aldehyde and ammonia. It has undergone many modifications and improvements and is now the method of choice for fast access to DHP derivatives, which are useful for various bioactivities such as calcium channel blockers and antihypertensive agents [ 10 , 46 ] but, also, as scaffolds in medicinal chemistry [ 14 ]. Under oxidative conditions, these so-called Hantzsch esters can be transformed into the corresponding pyridines, a strategy used to prepare single regio-isomers of poly-substituted pyridines [ 47 , 48 , 49 ] ( Scheme 9 ).…”

“…Most MCRs are mediated by a variety of catalysts [ 12 , 13 , 14 ]. Although many of them are important industrial organic reactions, the development of biocatalytic MCRs has only recently attracted the interest of organic chemists [ 15 ].…”

Total phenolic content, cyclooxygenases, ?-glucosidase, acetylcholinesterase, tyrosinase inhibitory and DPPH radical scavenging effects of Cornus sanguinea leaves and fruits

“…The DPPH radical scavenging effects of the extracts were carried out according to our previous study with slight modification [33]. Gallic acid was used as a positive control and methanol (1%) was used as blank.…”

Fused 1,4‐Dihydropyridines and Their Corresponding Pyridines: Synthesis, Molecular Modeling and Cholinesterase Inhibition

“…The use of some of these inhibitors such as tacrine causes hepatotoxicity, in turn, resulting in increasing side effects [5] . These side effects make researchers tend to design and synthesize new drugs to have fewer side effects [6] …”