Metal pyrimidine complexes (MPCs) including cadmium-barbiturate (Cd-BA), zinc-barbiturate (Zn-BA), cadmium-thiouracil (Cd-TU) and mercury-thiouracil (Hg-TU) were prepared and their analysis was carried out. These MPCs were evaluated as monoamine oxidase-B (MAO-B) inhibitors. Rat brain MAO-B was inhibited (in vitro) by Cd-BA, Zn-BA, Cd-TU and Hg-TU complexes. The inhibition of MAO-B by these complexes was time and concentration dependent. The values of IC50 of Zn-BA, Cd-BA, Hg-TU and Cd-TU were 10.2, 15.8, 16.2 and 20.4 nM, respectively. The effect of different substrate concentrations in the absence and in the presence of MPCs was determined. Lineweaver-Burk plots were plotted and the values of apparent Michaelis constant (Km), maximum velocity (Vmax), the dissociation constant of enzyme inhibitor complex (Ki) and the percent of inhibition (i%) were calculated. The data showed that the inhibition of MAO-B by all studied MPCs was the non-competitive type. The sequence of inhibition zone was: Zn-BA>Cd-BA and Hg-TU>Cd-TU affected by the chemistry of both the metal and the ligand. Otherwise, the results of the present study showed that the inhibition of MAO-B by all MPCs was fully reversible. The data showed that the presence of Cd-BA, Zn-BA, Cd-TU and Hg-TU complexes changed the optimum temperature and pH of MAO-B.
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http://dx.doi.org/10.1016/j.cbi.2013.11.012 | DOI Listing |
Theranostics
January 2025
Division of Cancer Biology, Laboratory Animal Center, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Bone metastasis and skeletal-related complications are primary causes of mortality in advanced-stage prostate cancer (PCa). Epigenetic regulation, particularly histone modification, plays a key role in this process; however, the underlying mechanisms remain elusive. In mouse models, JARID1D was an important mediator of both visceral and bone metastases.
View Article and Find Full Text PDFMol Neurodegener
January 2025
Center for Cognition and Sociality, Life Science Institute (LSI), Institute for Basic Science (IBS), Daejeon, Republic of Korea.
Background: Alzheimer's Disease (AD) is a neurodegenerative disease with drastically altered astrocytic metabolism. Astrocytic GABA and HO are associated with memory impairment in AD and synthesized through the Monoamine Oxidase B (MAOB)-mediated multi-step degradation of putrescine. However, the enzymes downstream to MAOB in this pathway remain unidentified.
View Article and Find Full Text PDFCurr Neuropharmacol
January 2025
Department of Stem Cell Bioengineering, Mossakowski Medical Research Institute, Polish Academy of Sciences, Pawinskiego 5 Str, 02-106 Warsaw, Poland.
The purpose of this review was to analyse the literature regarding the correlation between the level of tryptamine, aryl hydrocarbon receptor (AHR) signalling pathway activation, and monoamine oxidase (MAO)-A and MAO-B activity in health and conditions such as neurodegenerative, neurodevelopmental, and psychiatric disorders. Tryptamine is generated through the decarboxylation of tryptophan by aromatic amino acid decarboxylase (AADC) in the central nervous system (CNS), peripheral nervous system (PNS), endocrine system, and gut bacteria. Organ-specific metabolism of tryptamine, which is mediated by different MAO isoforms, causes this trace amine to have different pharmacokinetics between the brain and periphery.
View Article and Find Full Text PDFACS Med Chem Lett
January 2025
Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra 425405, India.
Linezolid, a widely used oxazolidinone antibiotic, exhibits potent activity against resistant bacterial infections but is associated with serotonergic toxicity, primarily due to its inhibition of monoamine oxidase (MAO). MAOs, consisting of MAO-A and MAO-B isoforms, play crucial roles in neurotransmitter metabolism, with implications for neurodegenerative disorders like Parkinson's and Alzheimer's diseases. This study aims to optimize Linezolid's structure to transform it into a selective MAO-B inhibitor.
View Article and Find Full Text PDFAlzheimer's disease (AD) is the most prevalent neurodegenerative dementia, marked by progressive cognitive decline and memory impairment. Despite advances in therapeutic research, single-target-directed treatments often fall short in addressing the complex, multifactorial nature of AD. This arises from various pathological features, including amyloid-β (Aβ) aggregate deposition, metal ion dysregulation, oxidative stress, impaired neurotransmission, neuroinflammation, mitochondrial dysfunction, and neuronal cell death.
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