- |||||||||| Cognex (tacrine) / Shionogi
Preclinical, Journal: Effects of Vindoline on rat cytochrome P450 isoforms activities in vitro. (Pubmed Central) - Jul 23, 2022
IC50 values of CYP1A2, CYP2B, CYP2C11, CYP2D1 and CYP3A were 113.4 μmol·L , 83.78 μmol·L , 22.50 μmol·L , 9.081 μmol·L and 52.76 μmol·L , respectively. The in vitro results demonstrated that vindoline could inhibit CYP2D1 activity in rats, and weak inhibitory effect on CYP2C11 and CYP3A, but had no obvious effects on CYP1A2 and CYP2B.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: 4-Aminoquinoline-Based Adamantanes as Potential Anticholinesterase Agents in Symptomatic Treatment of Alzheimer's Disease. (Pubmed Central) - Jun 25, 2022
The tested compounds displayed modest but generally higher antioxidant activity than the structurally similar AD drug tacrine...Among them, two compounds stand out: compound 5 as the most potent inhibitor of both cholinesterases with a K constant in low nano molar range and the potential to cross the BBB, and compound 8, which met all our requirements, including high cholinesterase inhibition, good oral bioavailability, and antioxidative effect. The QSAR model revealed that AChE and BChE inhibition was mainly influenced by the ring and topological descriptors MCD, Nnum, RP, and RSIpw3, which defined the shape, conformational flexibility, and surface properties of the molecules.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: Selenourea and thiourea derivatives of chiral and achiral enetetramines: Synthesis, characterization and enzyme inhibitory properties. (Pubmed Central) - Jun 14, 2022
The results indicated that all the synthesized compounds exhibited excellent inhibitory activities against mentioned enzymes as compared with standard inhibitors. Representatively, the most potent compound against α-glycosidase enzyme, (S,S)-5b, was 12-times more potent than standard inhibitor acarbose; 7b and 8a as most potent compounds against cholinesterase enzymes, were around 5 and 13-times more potent than standard inhibitor tacrine against achethylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively.
- |||||||||| Cognex (tacrine) / Shionogi
Review, Journal: Determination of Anti-Alzheimer's Disease Activity of Selected Plant Ingredients. (Pubmed Central) - Jun 5, 2022
This study also aims to highlight species with assessed efficacy, usable plant parts and the most active plant components in order to identify species and compounds of interest for further study. Future research directions are suggested and recommendations made to expand the use of medicinal plants, their formulations and plant-derived active compounds to prevent, mitigate and treat Alzheimer's disease.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: Crystal structure of human acetylcholinesterase in complex with tacrine: Implications for drug discovery. (Pubmed Central) - Jun 4, 2022
The conformational heterogeneity of tacrine within the electron density was addressed with the help of molecular mechanics assisted methods and the low-energy ligand configuration is reported, which provides a mechanistic explanation for the high binding affinity of tacrine towards AChE. Additionally, structural comparison of reported hAChE structures sheds light on the conformational selection and induced fit effects of various active site residues upon binding to different ligands and provides insight for future drug design campaigns against AD where AChE is a drug target.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: Robotised Geometric Inspection of Thin-Walled Aerospace Casings. (Pubmed Central) - May 29, 2022
Laser profilometers from two brands, Cognex and Keyence, were used to measure...The obtained solutions were compared and verified in accordance with the requirements of the manufacturer Pratt and Whitney Rzeszów S.A. The results of the work indicated that correct solutions were obtained with a very large reduction in control time. In addition, the measurement is fully automated and transferable to the company's electronic systems.
- |||||||||| Cognex (tacrine) / Shionogi
Preclinical, Journal: Evaluation of anti-amnesic effect of Conyza bonariensis in rats. (Pubmed Central) - May 22, 2022
Thus, the new conjugates have displayed the potential to be multifunctional anti-AD agents for further development. The results indicated that PECB might be a potential curative drug for the treatment of cognitive impairment.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: Development of Neuropeptide Y and Cell-Penetrating Peptide MAP Adsorbed onto Lipid Nanoparticle Surface. (Pubmed Central) - May 21, 2022
Several non-covalent interactions appear to be involved in peptide adsorption with the possibility of three adsorption peptide hypothesis that may occur with NLC in solution. Moreover, and for the first time, in silico docking analysis demonstrated strong interaction between CPP MAP and NPY Y1 receptor with high score values when compared to standard antagonist and NPY.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: New benzamide derivatives and their nicotinamide/cinnamamide analogs as cholinesterase inhibitors. (Pubmed Central) - May 6, 2022
The most active compounds B4 (IC50: 15.42 nM), N4 (IC50: 12.14 nM), and C4 (IC50: 10.67 nM) in each series towards AChE were docked at the binding site of AChE enzyme to explain the inhibitory activities of each series. On the other hand, the compounds B4, N4, and C4 showed satisfactory pharmacokinetic properties via the prediction of ADME profiles.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: Acetylcholinesterase Enzyme Inhibitor Molecules with Therapeutic Potential for Alzheimer's Disease. (Pubmed Central) - May 6, 2022
This review comprises the many hybrids and non-hybrid forms of heteroaromatic and non-heteroaromatic compounds that were designed and evaluated for AchE inhibition by Ellman's method of assay. These novel compounds may assist the future perspectives in the discovery of novel moieties against Alzheimer's disease by the inhibition of AchE.
- |||||||||| Cognex (tacrine) / Shionogi
Preclinical, Journal: New 4-phenylpiperazine-carbodithioate-N-phenylacetamide hybrids: Synthesis, in vitro and in silico evaluations against cholinesterase and α-glucosidase enzymes. (Pubmed Central) - May 6, 2022
The obtained results showed that most of the synthesized compounds exhibited high to good anti-AChE and anti-BChE activity in the range of nanomolar concentrations in comparison to tacrine as a positive control...Moreover, all the newly synthesized compounds 6a-n had significant K values against α-glucosidase when compared with the positive control acarbose...This compound also fitted in the α-glucosidase active site and interacted with key residues. An in silico study of the druglikeness/absorption, distribution, metabolism, and excretion (ADME)/toxicity profile of the selected compounds 6e, 6i, and 6l predicts that these compounds are drug-like and have the appropriate properties in terms of ADME and toxicity.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: Benzimidazolium salts bearing the trifluoromethyl group as organofluorine compounds: Synthesis, characterization, crystal structure, in silico study, and inhibitory profiles against acetylcholinesterase and α-glycosidase. (Pubmed Central) - Apr 20, 2022
Likewise, as a result of the same compounds against the α-Gly enzyme, the compound 3d had the highest binding affinity (-8.39 kcal/mol) between the four selected compounds and the positive control (-8.27, -8.10, -8.06, and -7.53 kcal/mol for 3f, 3e, 2e, and acarbose, respectively). From the absorption, distribution, metabolism, excretion, and toxicity analyses, it can be concluded that the compounds under consideration exhibited more drug-likeness properties in the prediction studies compared to positive controls.
- |||||||||| donepezil / Generic mfg.
Review, Journal: Exploration of Potent Multi-Target-Directed-Ligands as Anti-Alzheimer's Disease Agents: A Moiety Based Review. (Pubmed Central) - Apr 7, 2022
Hence, the community of scientists are rigorously working on multi-target-directed agents that incorporate two or more active scaffolds in one compound or hybrid of active moieties. This article aims at the evaluation of novel potential compounds and moieties such as quinolines, chalcones, coumarins, chromenes, piperazine, carbazoles, cinnamic acids, tacrine hybrids, donepezil hybrids and so on that have been introduced as multi-target-directed agents in recent five years.
- |||||||||| donepezil / Generic mfg.
Journal: A Comprehensive 2D-LC/MS Online Platform for Screening of Acetylcholinesterase Inhibitors. (Pubmed Central) - Apr 5, 2022
We systematically investigated the effects of method parameters that are of practical significance and are known to affect the enzyme assay and interfere in the analysis such as: bioreactor dimensions, loop sizes, amount of immobilized enzyme, second dimension flow rates, reaction time, substrate concentration, presence of organic modifier, limit of detection and signal suppression. The performance of this new platform was evaluated using a mixture containing three known AChE inhibitors (tacrine, galanthamine and donepezil) and an ethanolic extract obtained from the dry bulbs of Hippeastrum calyptratum (Amaryllidaceae) was investigated to provide a proof of concept of the applicability of the platform for the analysis of complex mixtures such as those derived from NPs.
- |||||||||| donepezil / Generic mfg.
Journal: Multi-Target Directed Ligands (MTDLs): Promising Coumarin Hybrids for Alzheimer's Disease. (Pubmed Central) - Apr 2, 2022
In the present review, we have focused on different reported coumarin hy- brids as multi-target-directed agents against AD. These include hybrids of coumarin with carbazole, benzofuran, dithiocarbamate, quinoline, pargyline, tacrine, N-benzyl pyridinium, donepezil, purine, piperidine, morpholine, aminophenol, benzylamino, halophenylalkylamidic, thiazole, thiourea, hy- droxypyridinone, triazole, piperazine, chalcone, etc. Along with the therapeutic potentials of these hy- brids, important clinical investigations and the structure-activity relationship has also been discussed in this compilation.
- |||||||||| donepezil / Generic mfg.
Journal: Synthesis, biological evaluation, and molecular modeling simulations of new heterocyclic hybrids as multi-targeted anti-Alzheimer's agents. (Pubmed Central) - Mar 4, 2022
Structure modifications were performed to 9-amino function of THA core of tacrine and the pyrazolopyridine scaffolds linked to a variety of cyclic secondary amines directly or using amide spacers or ethylamine bridge or engaging THA with pyrazolopyridine to produce hybrid compounds...Compounds 16 and 28 proved to be multimodal anti-AD agents as they were potent hAChE inhibitors, in addition, they could bind with the amino acids of the peripheral anionic site (PAS) affecting Aβ aggregation and hence Aβ-dependent neurotoxicity especially compound 16 which was almost twofold more active than donepezil...Compound 28 had superior privilege by its dual ChE activity resulting in better cognitive improvement. Compounds 16 and 28 showed acceptable relative safety upon hepG2 cell line and excellent BBB penetration with wide safety margin as their LD were higher than 120 mg/kg.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: Novel metabolic enzyme inhibitors designed through the molecular hybridization of thiazole and pyrazoline scaffolds. (Pubmed Central) - Mar 3, 2022
Compounds 4a-k were also evaluated for their cytotoxic effects on the L929 mouse fibroblast (normal) cell line. Moreover, a comprehensive ligand-receptor interaction prediction was performed using the ADME-Tox, Glide XP, and MM-GBSA modules of the Schrödinger Small-Molecule Drug Discovery Suite to elucidate the potential binding modes of the new hybrid inhibitors against these metabolic enzymes.
- |||||||||| abiraterone acetate / Generic mfg., nifedipine immediate release / Generic mfg.
Review, Journal: The Expanding Role of Pyridine and Dihydropyridine Scaffolds in Drug Design. (Pubmed Central) - Feb 2, 2022
This review examines the prospects of highly potent bioactive molecules to emphasize the advantages of using pyridine and dihydropyridine in drug design. We cover the most recent developments from 2010 to date, highlighting the ever-expanding role of both scaffolds in the field of medicinal chemistry and drug development.
- |||||||||| Cognex (tacrine) / Shionogi
Review, Journal: A systematic review of carbohydrate-based bioactive molecules for Alzheimer's disease. (Pubmed Central) - Feb 1, 2022
Most importantly, several reported carbohydrate-based molecules for Alzheimer's disease act on β-amyloid aggregation, tau protein, cholinesterase and oxidative stress, with enhanced pharmacokinetic and mechanistic properties. The prospect of designing carbohydrate-based molecules for Alzheimer's disease will definitely provide potential opportunities to discover novel carbohydrate-based drugs.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: Targeting INMT and interrupting its methylation pathway for the treatment of castration resistant prostate cancer. (Pubmed Central) - Feb 1, 2022
The prospect of designing carbohydrate-based molecules for Alzheimer's disease will definitely provide potential opportunities to discover novel carbohydrate-based drugs. Our study suggests that INMT drives PCa castration resistance through detoxification of anticancer metabolites, targeting INMT or its regulator SMYD3 or/and its methylation metabolites represents an effective therapeutic avenue for CRPC treatment.
- |||||||||| hyoscine butylbromide oral / Generic mfg.
Journal: NLX-101, a cortical 5-HT receptor biased agonist, reverses scopolamine-induced deficit in the delayed non-matching to position model of cognition. (Pubmed Central) - Jan 26, 2022
Moreover, NLX-101 (0.04 and 0.16 mg/kg) dose-dependently and significantly opposed scopolamine-induced impairment for 5 and 10 s delays, with near-total reversal at 10 s. The acetylcholinesterase inhibitor, tacrine, also opposed scopolamine-induced impairment but was less potent and efficacious, with a single significant effect at 2.5 mg/kg and 5 s delay only. The present data suggest that biased agonism at post-synaptic, cortical 5-HT receptors could prove useful in neurological or neuropsychiatric pathologies characterized by cognitive deficits consecutive to a reduced central cholinergic tone.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: Peroxidase-like activity of Ru-N-C nanozymes in colorimetric assay of acetylcholinesterase activity. (Pubmed Central) - Jan 18, 2022
Taking advantages of the remarkable peroxidase-mimicking activity, outstanding stability and reusability of Ru-N-C nanozymes, a novel biosensing system with explicit mechanism is strategically fabricated for sensitively determining acetylcholinesterase (AChE) and tacrine...Furthermore, "INH" and "IMPLICATION-AND" logic gates are rationally constructed based on the proposed colorimetric sensor. This work not only provides one sustainable and effective avenue to fabricate Ru-N-C-based peroxidase mimic with high catalytic performance, and also gives new impetuses for developing novel biosensors by applying Ru-N-C-based enzyme mimics as substitutes for the natural enzyme.
- |||||||||| Cognex (tacrine) / Shionogi
Journal: Multi-target drug design of anti-Alzheimer's disease based on tacrine. (Pubmed Central) - Jan 15, 2022
Additionally, the tacrine-based MTDLs can also be designed on the basis of other theories of AD, for example, introducing functional moieties to modulate the formation of β-amyloid (Aβ), oxidation resistance or metal chelation. In this paper, the research progress of tacrine-based MTDLs is summarized.
- |||||||||| donepezil / Generic mfg., galantamine hydrobromide / Generic mfg.
Clinical, Review, Journal: Efficacy of acetylcholinesterase inhibitors in Alzheimer's disease. (Pubmed Central) - Jan 12, 2022
Other approaches in which ChE-Is were investigated is in their use in combination with other classes of drugs such as cholinergic precursors, N-methyl-d-aspartate (NMDA) receptor antagonists and antioxidant agents. After many years from the introduction in therapy of ChE-Is, the combination with other classes of drugs may represent the chance for a renewed interest of ChE-Is in the treatment of adult-onset dementia disorders.
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