A simple, efficient and green approach for the synthesis of spiro-dihydropyridines derivatives by one-pot multi-component reaction of isatin or acenaphthoquinone derivatives (1 equiv) with malononitrile (1 equiv) and N,N'-substituted-2-nitroethene-1,1-diamines (1 equiv) in PEG-400 under catalyst-free conditions is described. This method provides several advantages such as environmental friendliness, short reaction time, and simple workup procedure for the synthesis of biologically important compounds. The ability of synthesized compounds in inhibition of acetyl and butyrylcholinesterase were investigated both in vitro and in silico. All compounds showed moderate to high level activity against both acetyl and butyrylcholinesterase. There was a good correlation between in vitro and in silico studies.
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http://dx.doi.org/10.1016/j.bmc.2016.02.019 | DOI Listing |
J Enzyme Inhib Med Chem
December 2024
Faculty of Food and Technology Osijek, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia.
The growing prevalence of Alzheimer's disease calls for a drug that can simultaneously act towards several targets involved in the pathophysiology of the disease. In our study, we evaluated the potential of hydrazone and -acylhydrazone derivatives of vitamin B6 and pyridine-4-carbaldehyde to be used as multi-target directed ligands targeting cholinergic system by inhibiting acetyl- and butyrylcholinesterase, lowering the accumulation of β-amyloid plaques by inhibiting both the β-secretase activity and amyloid self-aggregation, and maintaining the biometal balance by chelating certain biometals. Our results showed that all of the tested hydrazones were potent inhibitors of human cholinesterases with inhibition constants (i) in micromolar range able to lower the activity of β-secretase, inhibit amyloid aggregation, chelate biometals and act as antioxidants.
View Article and Find Full Text PDFEnviron Sci Pollut Res Int
December 2024
IIIA-UNSAM-CONICET, Instituto de Investigación E Ingeniería Ambiental, Escuela de Hábitat y Sostenibilidad (EHyS), Universidad Nacional de San Martín (UNSAM), Av. 25 de Mayo 1021 (CP. 1650), Buenos Aires, Argentina.
The release in aquatic environments of emergent contaminants such as copper oxide nanoparticles (CuO-NPs) has generated concerns on their short- and long-term toxicity and the potential risk for more vulnerable animal groups, such as amphibians. In this sense, the aim of this work was to evaluate the toxicity of CuO-NPs in comparison with its respective salt (CuCl) in embryos and larvae of a native amphibian, Rhinella arenarum, by acute (96 h) and chronic (504 h) standardized bioassays. Lethality and sublethal effects such as developmental, morphological, and ethological alterations were assessed in a wide range of concentrations (0.
View Article and Find Full Text PDFNat Prod Res
November 2024
Department of Chemistry, Faculty of Science, Mugla Sitki Kocman University, Mugla, Turkey.
The genus L. has been used in the treatment of rheumatic, diabetic and ulcerous diseases. Herein, the antioxidant, anticholinesterase, and antidiabetic activities of Griseb.
View Article and Find Full Text PDFPhytother Res
January 2025
Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Pozzuoli (NA), Italy.
Cannabidiolic (CBDA) and cannabigerolic (CBGA) acids are naturally occurring compounds from Cannabis sativa plant, previously identified by us as dual PPARα/γ agonists. Since the development of multitarget-directed ligands (MTDL) represents a valuable strategy to alleviate and slow down the progression of multifactorial diseases, we evaluated the potential ability of CBDA and CBGA to also inhibit enzymes involved in the modulation of the cholinergic tone and/or β-amyloid production. A multidisciplinary approach based on computational and biochemical studies was pursued on selected enzymes, followed by behavioral and electrophysiological experiments in an AD mouse model.
View Article and Find Full Text PDFBioorg Med Chem
December 2024
Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA; Center of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Institute for Computational Discovery and Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Michigan Institute for Data and AI in Society, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
A series of 2-arylhydrazinylidene-3-oxo acids (AHOAs) was prepared by dealkylation of alkyl-2-arylhydrazinylidene-3-oxo-3-alkanoates with AlBr. Using X-Ray, NMR spectroscopy, and quantum mechanical calculations (QM), the existence of AHOAs in a thermodynamically favorable Z-form stabilized by two intramolecular H-bonds was established. All AHOAs had acceptable ADME parameters.
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