MAO-B

Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome and (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2 H )-one ( 1 ), aryl(or heteroaryl)glyoxal monohydrates ( 2a - h ), and hydrazine monohydrate (NH2 NH2 •H2 O) for the regioselective preparation of some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[ h ]cinnoline derivatives ( 3a - h )...

Aedes albopictus, a virus-vector pest, is primarily controlled through the use of insecticides. In this study, we investigated the mechanisms of resistance in Ae. albopictus in terms of chlorpyrifos neurotoxicity to Ae. albopictus and its effects on the olfactory system. We assessed Ca2+ -Mg2+ -ATP levels, choline acetyltransferase (ChAT), Monoamine oxidase (MAO), odorant-binding proteins (OBPs), and olfactory receptor (OR7) gene expression in Ae. albopictus using various assays including Y-shaped tube experiments and DanioVision analysis to evaluate macromotor behavior...

BACKGROUND: Hypometabolism tied to mitochondrial dysfunction occurs in the aging brain and in neurodegenerative disorders, including in Alzheimer's disease, in Down syndrome, and in mouse models of these conditions. We have previously shown that mitovesicles, small extracellular vesicles (EVs) of mitochondrial origin, are altered in content and abundance in multiple brain conditions characterized by mitochondrial dysfunction. However, given their recent discovery, it is yet to be explored what mitovesicles regulate and modify, both under physiological conditions and in the diseased brain...

Limeum indicum has been widely utilized in traditional medicine but no experimental work has been done on this herb. The primary objective of this study was to conduct a phytochemical analysis and assess the multifunctional capabilities of aforementioned plant in dual therapy for Alzheimer's disease (AD) and Type 2 diabetes (T2D). The phytochemical screening of ethanol, methanol extract, and their derived fractions of Limeum indicum was conducted using GC-MS, HPLC, UV-analysis and FTIR. The antioxidant capacity was evaluated by DPPH method...

Results pertaining to the mechanism of the oxidation of the tertiary amine 1-methyl-4-(1-methyl-1-H-pyrrol-2-yl)-1,2,3,6-tetrahydropyridine (MMTP, a close analog of the Parkinsonism inducing compound MPTP) by 3-methyllumiflavin (3MLF), a chemical model for the FAD cofactor of monoamine oxidase, are reported. MMTP and related compounds are among the few tertiary amines that are monoamine oxidase B (MAO-B) substrates. The MMTP/3MLF reaction is catalytic in the presence of O2 and the results under anaerobic conditions strongly suggest the involvement of radical intermediates, consistent with a single electron transfer mechanism...

AIM: The purpose of the current study was to explore the virtual library for the screening against Monoamine oxidase (MAO) isoforms. An in-house library of natural based ligands was docked within the active sites of MAO isoforms and their in vitro study was also conducted. OBJECTIVE: The prime objective of the current study was to screen and validate the natural-based derivatives for MAO inhibitory action with the least adverse effects and get molecular aspects about further structural modifications on the most active leads...

Reactive astrogliosis accompanies the two neuropathological hallmarks of Alzheimer's disease (AD)-Aβ plaques and neurofibrillary tangles-and parallels neurodegeneration in AD and AD-related dementias (ADRD). Thus, there is growing interest in developing imaging and fluid biomarkers of reactive astrogliosis for AD/ADRD diagnosis and prognostication. Monoamine oxidase-B (MAO-B) is emerging as a target for PET imaging radiotracers of reactive astrogliosis. However, a thorough characterization of MAO-B expression in postmortem control and AD/ADRD brains is lacking...

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Monoamine oxidases (MAOs) inhibitors could decrease reactive oxygen species (ROS) generation, enhance mono-aminergic neural transmission, and have major therapeutic benefits for the treatment of Alzheimer's disease (AD). Following the conjunction of ferulic acid (FA)/gallic acid (GA) with sulfonamide, alanine and 2-aminobenzothiazole, we planned to assess the radical scavenging and antioxidant properties of synthesized analogs by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP) assays...

Reactive astrocytes play an important role in the development of Alzheimer's disease (AD). Here, we aimed to investigate the temporospatial relationships among monoamine oxidase-B, tau and amyloid-β (Aβ), translocator protein, and glucose metabolism by using multitracer imaging in AD transgenic mouse models. Positron emission tomography (PET) imaging with [18 F]SMBT-1 (monoamine oxidase-B), [18 F]florbetapir (Aβ), [18 F]PM-PBB3 (tau), [18 F]fluorodeoxyglucose (FDG), and [18 F]DPA-714 (translocator protein) was carried out in 5- and 10-month-old APP/PS1, 11-month-old 3×Tg mice, and aged-matched wild-type mice...

Alzheimer's disease (AD) is a multifactorial irreversible neurological disorder with multiple enzymes involved. In the treatment of AD, multifunctional agents targeting cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors have shown promising results. Herein, a series of novel quinoline-sulfonamides (a1-18) were designed and synthesized as a dual inhibitor of MAOs and ChEs. The in vitro results showed that compounds a5, a12, a11, and a6 exhibited the most potent compounds against specific enzymes. They had IC50 value 0...

In neurodegenerative diseases, using a single molecule that can exert multiple effects to modify the disease may have superior activity over the classical "one molecule-one target" approach. Herein, we describe the discovery of 6-hydroxybenzothiazol-2-carboxamides as highly potent and selective MAO-B inhibitors. Variation of the amide substituent led to several potent compounds having diverse side chains with cyclohexylamide 40 displaying the highest potency towards MAO-B (IC50  = 11 nM). To discover new compounds with extended efficacy against neurotoxic mechanisms in neurodegenerative diseases, MAO-B inhibitors were screened against PHF6, R3 tau, cellular tau and α-synuclein (α-syn) aggregation...

CONTEXT: Monoamine oxidase B (MAO-B), an enzyme of significant relevance in the realm of neurodegenerative disorders, has garnered considerable attention as a potential target for therapeutic intervention. Natural compounds known as chalcones have shown potential as MAO-B inhibitors. In this particular study, we employed a multimodal computational method to evaluate the inhibitory effects of chalcones on MAO-B. METHODS: Molecular docking methods were used to study and assess the complicated binding interactions that occur between chalcones and MAO-B...

Monoaminooxidases (MAOs) are important targets for drugs used in the treatment of neurological and psychiatric disorders and particularly on Parkinsońs Disease (PD). Compounds containing a trans-stilbenoid skeleton have demonstrated good selective and reversible MAO-B inhibition. Here, twenty-two (Z)-3-benzylidenephthalides (benzalphthalides, BPHs) displaying a trans-stilbenoid skeleton have been synthesised and evaluated as inhibitors of the MAO-A and MAO-B isoforms. Some BPHs have selectively inhibited MAO-B, with IC50 values ranging from sub-nM to μM...

In this study, a series of novel benzyloxybenzene substituted (S)-α-amino acid methyl esters and their amide derivatives were synthesized and evaluated for their inhibitory actions against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase A (MAO-A), and monoamine oxidase B (MAO-B). The synthetic strategy was based on starting from benzyl bromide (5) and 4-hydroxybenzaldehyde (6). The reaction of 5 and 6 in the presence of K2 CO3 gave benzyloxybenzaldehyde 7...

We report here the first dual inhibitors of brain carbonic anhydrases (CAs) and monoamine oxidase-B (MAO-B) for the management of Alzheimer's disease. Classical CA inhibitors (CAIs) such as methazolamide prevent amyloid-β-peptide (Aβ)-induced overproduction of reactive oxygen species (ROS) and mitochondrial dysfunction. MAO-B is also implicated in ROS production, cholinergic system disruption, and amyloid plaque formation. In this work, we combined a reversible MAO-B inhibitor of the coumarin and chromone type with benzenesulfonamide fragments as highly effective CAIs...

AIMS: Excessive influx of manganese (Mn) into the brain across the blood-brain barrier induces neurodegeneration. CYP1B1 is involved in the metabolism of arachidonic acid (AA) that affects vascular homeostasis. We aimed to investigate the effect of brain CYP1B1 on Mn-induced neurotoxicity. METHOD: Brain Mn concentrations and α-synuclein accumulation were measured in wild-type and CYP1B1 knockout mice treated with MnCl2 (30 mg/kg) and biotin (0.2 g/kg) for 21 continuous days...

Monoamine oxidase (MAO) catalyzes the oxidative deamination of monoamines with two isoforms, namely, MAO-A and MAO-B, in mitochondrial outer membranes. These two types of MAO-A and MAO-B participate in changes in levels of neurotransmitter such as serotonin (5-hydroxytryptamine) and dopamine. Selective MAO-A inhibitors have been targeted for anti-depression treatment, while selective MAO-B inhibitors are targets of therapeutic agents for Alzheimer's disease and Parkinson's disease. For this reason, study on the development of MAO inhibitors has recently become important...

The recent progress in the development of in vivo biomarkers is rapidly changing how neurodegenerative diseases are conceptualized and diagnosed and how clinical trials are designed today. Alzheimer's disease (AD) - the most common neurodegenerative disorder - is characterized by a complex neuropathology involving the deposition of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated tau proteins, accompanied by the activation of glial cells, i...

Monoamine oxidases (MAOs), specifically MAO-A and MAO-B, play important roles in the breakdown of monoamine neurotransmitters. Therefore, MAO inhibitors are crucial for treating various neurodegenerative disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). In this study, we developed a novel cheminformatics pipeline by generating three diverse molecular feature-based machine learning-assisted quantitative structural activity relationship (ML-QSAR) models concerning MAO-B inhibition...