Editor-in-Chief İlkay Küçükgüzel Associate Editor Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2019 , Vol 23 , Issue 4
Synthesis, characterization and investigation of cholinesterase enzyme inhibition and antioxidant activities of some 4-aryl-1,4-dihydropyridine derivatives
Hasan Erdinç SELLİTEPE1,İnci Selin DOĞAN1,Gamze EROĞLU2,Burak BARUT3,Arzu ÖZEL3
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey
2Department of Pharmacology, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey
3Department of Biochemistry, Faculty of Pharmacy, Karadeniz Technical University, Trabzon, Turkey
DOI : 10.12991/jrp.2019.168 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 1H-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-3,5- 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. Keywords : 1,4-Dihydropyridine; Hantzsch reaction; copper sulfate catalyst; boric acid/acetic acid catalyst; antioxidant activity; cholinesterase inhibitory effect
Marmara University