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Discovery of Novel Procaine‐Imidazole Derivative as Inhibitor of Monoamine Oxidase‐B for Potential Benefit in Parkinson's Disease
Author(s) -
Wu Jiane,
Liu Qionghua,
Hu Yuping,
Wang Wenhua,
Gao Xinming
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202002303
Subject(s) - monoamine oxidase b , monoamine oxidase , mptp , pharmacology , chemistry , imidazole , dopamine , enzyme , inhibitory postsynaptic potential , monoamine neurotransmitter , biochemistry , stereochemistry , medicine , dopaminergic , serotonin , receptor
The clinically utility of selective monoamine oxidase (MAO)‐B inhibitors in Parkinson disease is widely recognized due to significant improvement in altered motor function and long‐term benefit. Therefore, in the present study, a series of procaine‐imidazole was synthesized and subsequently evaluated for MAO‐A and MAO‐B inhibitory activity in an enzymatic assay. Comparative inhibitory activity suggest that, target compounds selectively inhibit MAO‐B, as compared to MAO‐A. Among the tested derivatives, compound 8 i (2‐(diethylamino)ethyl4‐(4‐(4‐fluorophenyl)‐2‐(4‐hydroxyphenyl)‐1H‐imidazol‐1‐yl)benzoate) selectively inhibited MAO‐B with IC 50 of 0.032±0.002 (selectivity index over MAO‐A=475). The anti‐Parkinson effect of compound 8 i was further evaluated in MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) induced animal model of PD. It has been found that, compound 8 i causes significant improvement in motor function of mice as revealed by motor behavioral assessment using the footprint and horizontal wire test. Compound 8 i also improved the level of anti‐oxidant enzymes in the striatum of animal brains. Our study demonstrated the development of procaine‐imidazole derivatives as potent and selective MAO‐B inhibitor as potential agent against PD.