Abstract
A new series of N-pyridyl-hydrazone derivatives was synthesized by using a simple and efficient method. The final compounds obtained were screened for their inhibitory potency against monoamine oxidase (MAO) A and B. The newly synthesized compounds 2a–2n specifically inhibited monoamine oxidases, displaying notably low IC50 values. Compounds 2i and 2j, with a CF3 and OH group on the 4-position of the phenyl ring, respectively, showed considerable MAO-A and MAO-B inhibitory activities. Compounds 2k, 2l and 2n, with N-methylpyrrole, furan and pyridine moieties instead of the phenyl ring, were the most powerful and specific inhibitors of MAO-A, with IC50 values of 6.12 μM, 10.64 μM and 9.52 μM, respectively. Moreover, these active compounds were found to be non-cytotoxic to NIH/3T3 cells. This study supports future studies aimed at designing MAO inhibitors to obtain more viable medications for neurodegenerative disorders, such as Parkinson’s disease.
Highlights
monoamine oxidase (MAO) exists in two isoforms, MAO-A and MAO-B, which have contrasting substrate specificity; MAO-A deaminates serotonin and norepinephrine, and MAO-B acts on phenylethylamine
MAO-B inhibitors are used as a part of the treatment for Alzheimer’s and Parkinson’s diseases, whereas MAO-A inhibitors are used as antidepressants and antianxiety agents [1,2]
Our results indicated that a large number of the synthesized compounds have powerful inhibitory effects against both MAO-A and MAO-B, with IC50 concentrations in the micromolar range; the effects following introduction of substituents of various sizes to the phenyl ring were evaluated
Summary
MAO exists in two isoforms, MAO-A and MAO-B, which have contrasting substrate specificity; MAO-A deaminates serotonin and norepinephrine, and MAO-B acts on phenylethylamine. Given the essential role of MAOs in the inactivation of neurotransmitters, the mechanism of action of MAO-A and MAO-B have been an imperative focus for the treatment of the pathologies of many neurodegenerative diseases. MAO-B inhibitors are used as a part of the treatment for Alzheimer’s and Parkinson’s diseases, whereas MAO-A inhibitors are used as antidepressants and antianxiety agents [1,2]. Investigations on MAO inhibitors have increased in the recent years owing to their restorative effect on mental health. Specific MAO-A inhibitors such as iproniazid, clorgyline and moclobemide exert invigoration and antianxiety action [3,4]. Specific MAO-B inhibitors, for example selegiline, rasagiline and lazabemide, complement treatments for Parkinson’s and Alzheimer’s disease [5]. The vast majority of the currently used MAO inhibitors, such as iproniazid and tranylcypromine, appear to initiate
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