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cholinesterase inhibitor

Javier E Ortiz, Adriana Garro, Natalia B Pigni, María Belén Agüero, German Roitman, Alberto Slanis, Ricardo D Enriz, Gabriela E Feresin, Jaume Bastida, Alejandro Tapia
BACKGROUND: In Argentina, the Amaryllidaceae family (59 species) comprises a wide variety of genera, only a few species have been investigated as a potential source of cholinesterases inhibitors to treat Alzheimer disease (AD). PURPOSE: To study the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the basic dichloromethane extracts (E) from Hieronymiella aurea, H. caletensis, H. clidanthoides, H. marginata, and H. speciosa species, as well as the isolated compounds from these plant extracts...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Archana S Gurjar, Mrunali N Darekar, Keng Yoon Yeong, Luyi Ooi
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple factors associated with its pathogenesis. Our strategy against AD involves design of multi-targeted 2-substituted-4,5-diphenyl-1H-imidazole analogues which can interact and inhibit AChE, thereby, increasing the synaptic availability of ACh, inhibit BuChE, relieve induced oxidative stress and confer a neuroprotective role. Molecular docking was employed to study interactions within the AChE active site. In silico ADME study was performed to estimate pharmacokinetic parameters...
February 2, 2018: Bioorganic & Medicinal Chemistry
Valeria Cavallaro, Yanina F Moglie, Ana P Murray, Gabriel E Radivoy
A series of thirty-three alkynyl and β-ketophosphonates were evaluated for their in vitro acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitory activities using Ellman's spectrophotometric method. None of the examined compounds inhibited AChE activity at tested concentrations while twenty-nine of them showed significant and selective inhibition of BChE with IC50 values between 38.60 µM and 0.04 µM. In addition, structure-activity relationships were discussed. The most effective inhibitors were the dibutyl o-methoxyphenyl alkynylphosphonate 3dc and dibutyl o-methoxyphenyl β-ketophosphonate 4dc...
February 7, 2018: Bioorganic Chemistry
Fahimeh Vafadarnejad, Mohammad Mahdavi, Elahe Karimpour-Razkenari, Najmeh Edraki, Bilqees Sameem, Mahnaz Khanavi, Mina Saeedi, Tahmineh Akbarzadeh
A novel series of coumarin-pyridinium hybrids were synthesized and evaluated as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using Ellman's method. Among synthesized compounds, 1-(3-fluorobenzyl)-4-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium bromide (7l) was found to be the most active compound toward AChE (IC50 = 10.14 µM), 1-(3-chlorobenzyl)-3-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium bromide (7g) and 1-(2,3-dichlorobenzyl)-3-((2-oxo-2H-chromene-3-carboxamido)methyl)pyridinium chloride (7h) depicted the best BChE inhibitory activity (IC50s = 0...
January 27, 2018: Bioorganic Chemistry
Nikolaos Kokras, Evangelia Stamouli, Ioannis Sotiropoulos, Everina A Katirtzoglou, Kostas T Siarkos, Georgia Dalagiorgou, Krystallenia I Alexandraki, Stavroula Coulocheri, Christina Piperi, Antonios M Politis
BACKGROUND: Clinical and preclinical studies firmly support the involvement of the inflammation in the pathogenesis of Alzheimer's disease (AD). Despite acetylcholinesterase inhibitors (AChEI) being widely used in AD patients, there is no conclusive evidence about their impact on the inflammatory response. METHODS: This study investigates peripheral proinflammatory cytokines (interferon gamma [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukins 1β [IL-1β] and 6 [IL-6]) by firstly comparing peripheral blood mononuclear cell (PBMC)-derived secretion in drug-naïve and AChEI-treated AD patients versus healthy controls...
February 7, 2018: Journal of Clinical Psychopharmacology
Dawid Panek, Anna Więckowska, Anna Pasieka, Justyna Godyń, Jakub Jończyk, Marek Bajda, Damijan Knez, Stanislav Gobec, Barbara Malawska
The complex nature of Alzheimer's disease calls for multidirectional treatment. Consequently, the search for multi-target-directed ligands may lead to potential drug candidates. The aim of the present study is to seek multifunctional compounds with expected activity against disease-modifying and symptomatic targets. A series of 15 drug-like various substituted derivatives of 2-(benzylamino-2-hydroxyalkyl)isoindoline-1,3-diones was designed by modification of cholinesterase inhibitors toward β-secretase inhibition...
February 7, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Carey N Pope, Stephen Brimijoin
Acetylcholinesterase (AChE, EC and butyrylcholinesterase (BChE, EC are related enzymes found across the animal kingdom. The critical role of acetylcholinesterase in neurotransmission has been known for almost a century, but a physiological role for butyrylcholinesterase is just now emerging. The cholinesterases have been deliberately targeted for both therapy and toxicity, with cholinesterase inhibitors being used in the clinic for a variety of disorders and conversely for their toxic potential as pesticides and chemical weapons...
January 30, 2018: Biochemical Pharmacology
Sengul Uysal, Abdurrahman Aktumsek, Carene M N Picot, Hamiyet Unuvar, Adriano Mollica, Milen I Georgiev, Gokhan Zengin, Mohamad Fawzi Mahomoodally
Extracts (methanol, ethyl acetate, and water) from Dianthus calocephalus Boiss. prepared by different extraction techniques (maceration, Soxhlet, and ultrasonication) were studied for possible inhibitory action against key enzymes (α-amylase, α-glucosidase, acetyl cholinesterase, butyryl cholinesterase, and tyrosinase). Antioxidant potential was established using a battery of assays and phenolic compounds profiled by RP-HPLC. Binding pose of tyrosinase with rutin was studied by means of molecular docking...
January 30, 2018: Food and Chemical Toxicology
Jie Zhu, Hongyu Yang, Yao Chen, Hongzhi Lin, Qi Li, Jun Mo, Yaoyao Bian, Yuqiong Pei, Haopeng Sun
The cholinergic hypothesis has long been a "polar star" in drug discovery for Alzheimer's disease (AD), resulting in many small molecules and biological drug candidates. Most of the drugs marketed for AD are cholinergic. Herein, we report our efforts in the discovery of cholinesterases inhibitors (ChEIs) as multi-target-directed ligands. A series of tacrine-ferulic acid hybrids have been designed and synthesised. All these compounds showed potent acetyl-(AChE) and butyryl cholinesterase(BuChE) inhibition. Among them, the optimal compound 10g, was the most potent inhibitor against AChE (electrophorus electricus (eeAChE) half maximal inhibitory concentration (IC50) = 37...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
Olga Prokopchuk, Barbara Grünwald, Ulrich Nitsche, Carsten Jäger, Oleksii L Prokopchuk, Elaine C Schubert, Helmut Friess, Marc E Martignoni, Achim Krüger
BACKGROUND: Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a candidate diagnostic and prognostic biomarker for pancreatic ductal adenocarcinoma (PDAC). Here, we determined the possible association of systemic TIMP-1 levels with cachexia and jaundice, two common PDAC-associated conditions. METHODS: Plasma TIMP-1 was measured by ELISA in patients diagnosed with PDAC (n = 36) and chronic pancreatitis (CP) (n = 25). Patients without pancreatic pathologies and known malignancies of other origin served as controls (n = 13)...
February 2, 2018: BMC Cancer
Ariana Gatt, Antigoni Ekonomou, Alyma Somani, Sandrine Thuret, David Howlett, Anne Corbett, Mary Johnson, Elaine Perry, Johannes Attems, Paul Francis, Dag Aarsland, Clive Ballard
OBJECTIVE: To examine the impact of selective serotonin reuptake inhibitors (SSRIs) and depression on neurogenesis and cognition in dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD). METHODS: Late-stage progenitor cells were quantified in the subgranular zone (SGZ) of the hippocampal dentate gyrus of DLB/PDD patients (n = 41) and controls without dementia (n = 15) and compared between treatment groups (unmedicated, SSRIs, acetyl cholinesterase inhibitors [AChEIs], combined SSRIs and AChEIs)...
January 27, 2018: Dementia and Geriatric Cognitive Disorders
Anna Więckowska, Tomasz Wichur, Justyna Godyń, Adam Bucki, Monika Marcinkowska, Agata Siwek, Krzysztof Więckowski, Paula Zaręba, Damijan Knez, Monika Głuch-Lutwin, Grzegorz Kazek, Gniewomir Latacz, Kamil Mika, Marcin Kołaczkowski, Jan Korabecny, Ondrej Soukup, Marketa Benkova, Katarzyna J Kiec-Kononowicz, Stanislav Gobec, Barbara Malawska
Alzheimer's disease (AD) is a major public health problem, which is due to its increasing prevalence and lack of effective therapy or diagnostics. Complexity of AD pathomechanism requires complex treatment e.g. multifunctional ligands targeting both causes and symptoms of the disease. Here, we present new multi-target-directed ligands combining pharmacophore fragments that provide blockade of serotonin 5-HT6 receptors, acetyl/butyrylcholinesterase inhibition, and amyloid β anti-aggregation activity. Compound 12 has displayed balanced activity as an antagonist of 5-HT6 receptors (Ki = 18 nM) and non-competitive inhibitor of cholinesterases (IC50hAChE = 14 nM, IC50eqBuChE = 22 nM)...
January 31, 2018: ACS Chemical Neuroscience
Marco Canevelli, Giuseppe Bruno, Carlo Vico, Valerio Zaccaria, Eleonora Lacorte, Ivo Iavicoli, Nicola Vanacore, Matteo Cesari
BACKGROUND: There is now a wide consensus at recognizing social and economic circumstances as main determinants of the individual's health status. Nevertheless, characteristics relating to socioeconomic status (SES) are poorly described in research reports. The aim of the present review was to verify if the SES of participants is adequately reported in interventional studies targeting Alzheimer's disease (AD), and to explore the impact of SES proxy measures on the efficacy of the considered medications...
January 30, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Angela Stefanachi, Francesco Leonetti, Leonardo Pisani, Marco Catto, Angelo Carotti
Many naturally occurring substances, traditionally used in popular medicines around the world, contain the coumarin moiety. Coumarin represents a privileged scaffold for medicinal chemists, because of its peculiar physicochemical features, and the versatile and easy synthetic transformation into a large variety of functionalized coumarins. As a consequence, a huge number of coumarin derivatives have been designed, synthesized, and tested to address many pharmacological targets in a selective way, e.g., selective enzyme inhibitors, and more recently, a number of selected targets (multitarget ligands) involved in multifactorial diseases, such as Alzheimer's and Parkinson's diseases...
January 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Mathilde François, Jonathan Sicsic, Nathalie Pelletier Fleury
BACKGROUND: The impact of adverse effects of drugs for dementia on the risk of hospitalization has not been much studied despite the impact of hospitalizations on cognitive decline. OBJECTIVE: To determine if the main adverse effects of cholinesterase inhibitors and memantine may be associated with excess of hospitalization and to quantify the subsequent impact on healthcare expenditures. METHODS: A representative sample of the French national health insurance beneficiaries aged 65 and older and suffering from dementia were included and followed from 2007 to 2014...
2018: Journal of Alzheimer's Disease: JAD
Chiara Gambardella, Daniela Nichino, Camillo Iacometti, Sara Ferrando, Carla Falugi, Marco Faimali
The brine shrimp Artemia was used as a model organism to test toxicity of several neuroactive pesticides (chlorpyrifos (CLP), chlorpyrifos oxon (CLP ox), diazinon (DZN), carbaryl (CBR)) following exposure to far below than lethal doses. Cysts were exposed to the pesticides in order to test a scenario similar to actual coastal environment contamination, by analyzing different responses. Cysts were rehydrated in water containing the pesticides at concentrations ranging from 10-11 to 10-5 M, for 72, 96 and 192 h, respectively...
January 12, 2018: Aquatic Toxicology
Angela M Moncaleano-Niño, Andrea Luna-Acosta, Maria Camila Gómez-Cubillos, Luisa Villamil, Michael J Ahrens
In the present study, the sensitivity and concentration dependence of three functionally-defined components of cholinesterase activity (total: T-ChE; eserine-sensitive: Es-ChE; and eserine-resistant: Er-ChE) were quantified in the gill, digestive gland and adductor muscle of the tropical cup oyster Saccostrea sp., following acute (96h) aqueous exposure to commercial formulations of the organophosphate (OP) insecticide chlorpyrifos and the neonicotinoid (NN) imidacloprid (concentration range: 0.1-100mg/L), as well as to dissolved cadmium and copper (concentration range: 1-1000μg/L)...
January 17, 2018: Ecotoxicology and Environmental Safety
Laura K Triantafylidis, Jenna S Clemons, Emily P Peron, John Roefaro, Kristin M Zimmerman
BACKGROUND: Case reports have demonstrated that dual use of cholinesterase inhibitors (ChIs) and urinary anticholinergics (UAChs) in older adults may be associated with delusions, aggression, changes in cognition, and anxiety, which typically resolve on drug discontinuation. Despite opposing mechanisms of action, these drugs continue to be co-prescribed. OBJECTIVE: This systematic review evaluates cognitive and functional outcomes of dual use of ChIs and UAChs and describes its prevalence...
January 19, 2018: Drugs & Aging
Juan Joseph Young, Mallika Lavakumar, Deena Tampi, Silpa Balachandran, Rajesh R Tampi
Background: Frontotemporal dementia (FTD) describes a cluster of neurocognitive syndromes that present with impairment of executive functioning, changes in behavior, and a decrease in language proficiency. FTD is the second most common form of dementia in those younger than 65 years and is expected to increase in prevalence as the population ages. This goal in our review is to describe advances in the understanding of neurobiological pathology, classification, assessment, and treatment of FTD syndromes...
January 2018: Therapeutic Advances in Psychopharmacology
Hiroshi Yamawaki, Seiji Futagami, Mako Wakabayashi, Noriko Sakasegawa, Shuhei Agawa, Kazutoshi Higuchi, Yasuhiro Kodaka, Katsuhiko Iwakiri
Patients with functional dyspepsia, defined in the 2016 Rome IV criteria as bothersome clinical dyspepsia symptoms, experience markedly reduced quality of life. Several etiologies have been associated with the disorder. In the Rome IV criteria, the brain-gut axis was acknowledged as an important factor in the etiology of functional gastrointestinal (GI) disorders. The distinct subgroups of functional dyspepsia, epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), are treated differently: acid secretion inhibitors are recommended with patients with EPS, whereas prokinetic drugs as mosapride and acotiamide are recommended for patients with PDS...
January 2018: Therapeutic Advances in Chronic Disease
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