BACE

This study examines the synthesis and evaluation of 11 newly developed compounds as potential anti-Alzheimer's agents that occur via cholinesterase and β-secretase inhibition. The compounds were tested for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using the modified Ellman method. The results showed that several compounds exhibited significant inhibition of AChE, particularly compounds 6d, 7a, and 7e, which demonstrated high inhibitory activity at lower concentrations, with IC50 values of 0...

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 )...

A variety of cutting-edge methods and good knowledge of the illness's complex causes are causing a sea change in the field of Alzheimer's Disease (A.D.) research and treatment. Precision medicine is at the vanguard of this change, where individualized treatment plans based on genetic and biomarker profiles give a ray of hope for customized therapeutics. Combination therapies are becoming increasingly popular as a way to address the multifaceted pathology of Alzheimer's by simultaneously attacking Aβ plaques, tau tangles, neuroinflammation, and other factors...

PURPOSE: This retrospective study aimed to investigate the effectiveness and safety of bronchial arterial chemoembolization with drug-eluting beads (DEB-BACE) plus chemotherapy versus chemotherapy alone in patients with stage III and IV lung squamous cell carcinoma (LSCC) who are not appropriate candidates for radiochemotherapy. MATERIALS AND METHODS: In this retrospective analysis, we screened all adult patients undergoing either DEB-BACE plus chemotherapy or chemotherapy alone for stage III or IV LCSS at authors' center from January 2018 to August 2021...

BACKGROUND: Amyloid-β plaques (Aβ) are associated with Alzheimer's disease (AD). Pooled assessment of amyloid reduction in transgenic AD mice is critical for expediting anti-amyloid AD therapeutic research. OBJECTIVE: The mean threshold of Aβ reduction necessary to achieve cognitive improvement was measured via pooled assessment ( n  = 594 mice) of Morris water maze (MWM) escape latency of transgenic AD mice treated with substances intended to reduce Aβ via reduction of beta-secretase cleaving enzyme (BACE)...

Alzheimer's disease (AD) is the most common type of dementia and a significant concern to global public health due to the prevalence of aging populations. Donepezil is one of only a few medications approved for use as an anti-AD agent but all have adverse side effects. Reducing the dosage of AD drugs with plant extracts (phytotherapy) while maintaining efficacy is one strategy to minimize adverse side effects. We previously reported the anti-AD properties of an edible fern, Diplazium esculentum (Retz.) Sw. (DE), which inhibited key enzymes involved in AD pathogenesis including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-secretase 1 (BACE-1)...

Proton ceramic fuel cells offer numerous advantages compared with conventional fuel cells. However, the practical implementation of these cells is hindered by the poor sintering activity of the electrolyte. Despite extensive research efforts to improve the sintering activity of BCZY, the systematic exploration of the utilization of NiO as a sintering additive remains insufficient. In this study, we developed a novel BaCe0.55 Zr0.35 Y0.1 O3-δ (BCZY) electrolyte and systematically investigated the impact of adding different amounts of NiO on the sintering activity and electrochemical performance of BCZY...

Based on the biochemical understanding of Alzheimer's disease, here, we report the design, synthesis, and biological screening of a series of compounds against this neuro-disorder. Adopting the multitarget approach, the catalytic processes of BACE-1 and AChE were targeted, and thereby, compounds 15 , 22 , 25 , 26 , 27 , and 30 were identified with IC50 in the submicromolar range against these two enzymes. Further, compounds 15 and 25 displayed more than 50% inhibition of β-amyloid aggregation. Implying their physiological use, the compounds exhibited appreciable biological membrane permeability as observed through the parallel artificial membrane permeability experiment...

Chemically modified nucleosi(ti)des and functional oligonucleotides (ONs, including therapeutic oligonucleotides, aptamer, nuclease, etc.) have been identified playing an essential role in the areas of medicinal chemistry, chemical biology, biotechnology, and nanotechnology. Introduction of functional groups into the nucleobases of ONs mostly relies on the laborious de novo chemical synthesis. Due to the importance of nucleosides modification and aforementioned limitations of functionalizing ONs, herein, we describe a highly efficient site-selective alkylation at the C8-position of guanines in guanosine (together with its analogues), GMP, GDP, and GTP, as well as late-stage functionalization of dinucleotides and single-strand ONs (including ssDNA and RNA) through photo-mediated Minisci reaction...

Flavonoids are promising therapeutics for the treatment of Alzheimer's disease (AD). Therefore, it is of interest to study the anti-AD potential of 35 flavonoids towards the inhibition of AchE and BACE-1. Hence, the physicochemical, pharmacokinetic parameters, toxicity risk and drug-likeliness of the selected 35 flavonoids were computed. Further, the molecular docking analysis of flavonoids with AChE and BACE-1 were completed. A binding energy of -10.42 kcal/mol Epicatechin gallate, -10.16 kcal/mol sterubin and -10...

Alzheimer's disease (AD), a debilitating neurodegenerative condition, is characterized by progressive cognitive decline brought about by the deposition of amyloid beta (Aβ) plaques in the brain initiates downstream neuronal dysfunction and death in AD pathogenesis. The β-secretase (BACE-1) enzyme plays a crucial role in generating Aβ from amyloid precursor protein (APP). Hence, we report the virtual screening of marine phytochemicals as BACE-1 inhibitors. 2583 compounds, retrieved from Comprehensive Marine Natural Product Database (CMNPD), were primarily screened for drug-likeliness and blood-brain barrier permeability using admetSAR 2...

Convenient synthesis of stereochemically dense 5-oxo-pyrrolidines was obtained from succinic anyhdride and imines by combining the Castagnoli-Cushman reaction with directed Pd-catalyzed C(sp3 )-H functionalization, taking advantage of the developing carboxylic group properly derivatized with 8-aminoquinoline as a directing group. These fully substituted 5-oxopyrrolidines were found to be able to inhibit BACE-1 enzyme with sub-micromolar activity, thanks to the interaction of the key aryl appendage introduced by C(sp3 )-H activation within BACE-1 S2' subsite...

Accumulation of β-amyloid peptide (Aβ) induces neurotoxicity, which is the primary risk factor in the pathogenesis of Alzheimer's disease (AD). The cleavage of amyloid precursor protein (APP) by the β- (BACE) and γ- (PS1, PS2) secretases is a critical step in the amyloidogenic pathway. The induction of neuronal apoptosis by Aβ involves increased expression of B-cell lymphoma protein 2 (Bcl-2)-associated X (Bax) and decreased Bcl-2 expression. The seed of Carthamus tinctorius L...

BACKGROUND: The prognosis of back pain (BP) in the older adults is less favorable than in younger adults and progress to adverse outcomes and consequent worsening of health-related quality of life (HRQoL). The present study aimed to verify the association between BP intensity, disability and HRQoL in older adults residents in Brazil and Netherlands, and to evaluate whether the country of residence influences the associations. METHODS: Data were collected from 602 Brazilian and 675 Dutch participants with a new episode of BP from the Back Complaints in Elders (BACE) consortium...

Physical activity has been considered an important non-medication intervention in preserving mnemonic processes during aging. However, how aerobic exercise promotes such benefits for human health remains unclear. In this study, we aimed to explore the neuroprotective and anti-inflammatory effects of aerobic exercise against lipopolysaccharide (LPS)-induced amnesic C57BL/6J mice and BV-2 microglial cell models. In the in vivo experiment, the aerobic exercise training groups were allowed to run on a motorized treadmill 5 days/week for 4 weeks at a speed of 10 rpm/min, with LPS (0...

BACKGROUND: We have previously demonstrated that oxidative stress and brain mitochondrial dysfunction are key mediators of brain pathology during myocardial infarction (MI). <P> Objective: To investigate the beneficial effects of mitochondrial dynamic modulators, including mitochondrial fission inhibitor (Mdivi-1) and mitochondrial fusion promotor (M1), on cognitive function and molecular signaling in the brain of MI rats in comparison with the effect of enalapril. METHODS: Male rats were assigned to either sham or MI operation...

BACKGROUND: In the context of Greece, many instruments measuring constructs pertinent to child and adolescent mental health lacked a locally-validated, freely-available version. As part of a nationwide survey, we translated and cross-culturally adapted a collection of seventeen brief, largely-employed assessment tools that can be used at scale. METHODS: This study is part of the Child and Adolescent Mental Health Initiative in Greece (CAMHI), a capacity-building program focusing on enhancing mental health care for children and adolescents living in Greece...

No abstract text is available yet for this article.

ConspectusThe enzyme acetylcholinesterase (AChE) hydrolyzes the neurotransmitter acetylcholine (ACh) at cholinergic synapses of the peripheral and central nervous system. Thus, it is a prime therapeutic target for diseases that occur with a cholinergic deficit, prominently Alzheimer's disease (AD). Working at a rate near the diffusion limit, it is considered one of nature's most efficient enzymes. This is particularly meritorious considering that its catalytic site is buried at the bottom of a 20-Å-deep cavity, which is preceded by a bottleneck with a diameter shorter than that of the trimethylammonium group of ACh, which has to transit through it...

An efficient and promising method of treating complex neurodegenerative diseases like Alzheimer's disease (AD) is the multitarget-directed approach. Here in this work, a series of quinazoline derivatives ( AV-1 to AV-21 ) were rationally designed, synthesized, and biologically evaluated as multitargeted directed ligands against human cholinesterase (hChE) and human β-secretase (hBACE-1) that exhibit moderate to good inhibitory effects. Compounds AV-1 , AV-2 , and AV-3 from the series demonstrated balanced and significant inhibition against these targets...