<i>In Vitro</i> Enzyme Activity and Molecular Docking Studies of Pyrazoline Derivatives as Monoamine Oxidase Inhibitors
Sakarya, Mehtap Tugrak, Gul, Halise Inci, Yamali, Cem, Ozkay, Yusuf, Tok, Tugba Taskin
Monoamine oxidases (MAOs) are mitochondrial enzymes that catalyse the oxidative deamination of monoamine neurotransmitters and various xenobiotic amines in the central nervous system and peripheral tissues. They are of two types, MAO-A and MAO-B, which are different in terms of their substrates and tissue distributions. MAO-A oxidizes epinephrine, serotonin and norepinephrine, while MAO-B catalyzes the deamination of phenylethylamine and benzylamine. MAO-A inhibitors are used in the treatment of depression, while MAO-B inhibitors are used in the treatment of neurodegenerative diseases such as Parkinson's and Alzheimer diseases. MAO inhibitors are listed as the second choice in the treatment of major depression after selective serotonin reuptake inhibitors (SSRI) or tricyclic antidepressants. Various heterocyclic compounds with two or four nitrogen atoms have been used in the synthesis of selective and reversible MAO inhibitors for many years. In this study, the inhibitory effects of 2-(3-(4-methoxyphenyl)-5-aryl-4,5-dihydropyrazol-1-yl)benzo[d]thiazole compounds, having a 2-pyrazoline skeleton, on the MAO isoenzymes were investigated. Among the tested derivatives, compound 12 achieved IC50 values of 0.041 +/- 0.001 mM. The nature of inhibition was also determined to be non-competitive based on the Lineweaver-Burk plot. Molecular docking studies were also performed for compound 12, which is the most potent agent in the MAO-Aand MAO-B catalytic sites. The evaluation and explanation of the biological results at the atomic level with the positive compounds selected for each target are provided. Studies can be developed based on compound 12 as a candidate lead compound for further research as a non-competitive MAO-A and MAO-B inhibitor.
- Journal
- PHARMACEUTICAL CHEMISTRY JOURNAL
- Year
- 2024
- Volume
- 58
- Issue
- 3
- Pages
- 419-427
- ISSN
- 0091-150X
- eISSN
- 1573-9031
- DOI
- 10.1007/s11094-024-03161-7
- WoS UID
- WOS:001269310500001