Abstract:
:The inhibition of monoamine oxidase B (MAO-B) could be an effective approach for the treatment of various neurological disorders. In this study, a series of 1, 4-benzodioxan-substituted chalcone derivatives were designed, synthesised and evaluated for their inhibitory activity against human MAO-B (hMAO-B). The majority of these compounds showed inhibitory activity and high selectivity. The most potent compound, (E)-1-(3-bromo-4-fluorophenyl)-3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)prop-2-en-1-one (22), exhibited an IC50 of 0.026 µM with a selectivity index greater than 1538. Kinetics and reversibility studies confirmed that the representative active compounds acted as competitive and reversible inhibitors of hMAO-B. The enzyme-inhibitor interactions were investigated by molecular docking studies and the rationale was provided. As these potent hMAO-B inhibitors exhibited low neurotoxicity and possessed promising drug-like properties, we believe that these active compounds could be further investigated as potential drug candidates for future in vivo studies.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Kong Z,Sun D,Jiang Y,Hu Ydoi
10.1080/14756366.2020.1797711subject
Has Abstractpub_date
2020-12-01 00:00:00pages
1513-1523issue
1eissn
1475-6366issn
1475-6374journal_volume
35pub_type
杂志文章abstract::Quantitative structure-activity relationships (QSARs) within a series of cytochrome P450 2C9 (CYP2C9) and cytochrome P450 2C19 (CYP2C19) inhibitors are reported. In particular, it is noted that compound lipophilicity, in the form of log P values (where P is the octanol/water partition coefficient), is an important fac...
journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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abstract::Organophosphorus compounds pose a potential threat to both military and civilian populations. Since post-exposure therapy has its limitations, our research was focused on the possibility of improving pretreatment in order to limit the toxic effects of tabun. We determined the protective index of various combinations o...
journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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doi:10.3109/14756366.2015.1094468
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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更新日期:2015-06-01 00:00:00
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journal_title:Journal of enzyme inhibition and medicinal chemistry
pub_type: 杂志文章
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更新日期:2007-02-01 00:00:00
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journal_title:Journal of enzyme inhibition and medicinal chemistry
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更新日期:2016-08-01 00:00:00
abstract::We describe herein the design, multicomponent synthesis and biological studies of new donepezil + chromone + melatonin hybrids as potential agents for Alzheimer's disease (AD) therapy. We have identified compound 14n as promising multitarget small molecule showing strong BuChE inhibition (IC50 = 11.90 ± 0.05 nM), mode...
journal_title:Journal of enzyme inhibition and medicinal chemistry
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更新日期:2019-12-01 00:00:00