A series of new cyclopentaquinoline derivatives with 9-acridinecarboxylic acid and a different alkyl chain length were synthesized, and their ability to inhibit cholinesterases was evaluated. All designed compounds, except derivative , exhibited a selectivity for butyrylcholinesterase (BuChE) with IC values ranging from 103 to 539 nM. The derivative revealed the highest inhibitory activity towards BuChE (IC = 103.73 nM) and a suitable activity against AChE (IC = 272.33 nM). The derivative was the most active compound to AChE (IC = 113.34 nM) with satisfactory activity towards BuChE (IC = 203.52 nM). The potential hepatotoxic effect was evaluated for both and compounds. The and potential antioxidant activity was measured using the ORAC-FL method. The and derivatives revealed a significantly higher antioxidant potency, respectively 35 and 25 higher than tacrine. Theoretical, physicochemical, and pharmacokinetic properties were calculated using ACD Labs Percepta software. Molecular modeling and kinetic study were used to reveal the mechanism of cholinesterase inhibition in the most potent compounds: and .
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9179981 | PMC |
| http://dx.doi.org/10.3390/ijms23115876 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel multipotent conjugate bearing tacrine and donepezil motifs with dual cholinergic inhibition and neuroprotective properties targeting Alzheimer's disease.
RSC Med Chem
January 2025
Área de Neurofisiología celular, Instituto de Biología, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia Medellín Colombia
In this work, we developed potential multifunctional agents to combat Alzheimer's disease. According to our strategy, fragments of tacrine and donepezil were merged in a unique hybrid structure. After successfully synthesizing the compounds, they were evaluated for their dual AChE/BuChE inhibitor potential and neuroprotector response using a glutamate-induced excitotoxicity model.
View Article and Find Full Text PDFSpecific Rosetta-based protein-peptide prediction protocol allows the design of novel cholinesterase inhibitor peptides.
Bioorg Chem
January 2025
Laboratorio de Peptidos Bioactivos, Department of Organic Chemistry, Faculty of Biochemistry and Biological Sciences, National University of the Littoral, Ciudad Universitaria UNL, 3000 Santa Fe, Argentina; National Scientific and Technical Research Council (CONICET), Ministry of Science, Technology and Innovation, Godoy Cruz 2290, Ciudad de Buenos Aires, Argentina. Electronic address:
The search for novel cholinesterase inhibitors is essential for advancing treatments for neurodegenerative disorders such as Alzheimer's disease (AD). In this study, we employed the Rosetta pepspec module, originally developed for designing peptides targeting protein-protein interactions, to design de novo peptides targeting the peripheral aromatic site (PAS) of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). A total of nine peptides were designed for human AChE (hAChE), T.
View Article and Find Full Text PDFAlkaloid Profile, Anticholinesterase and Antioxidant Activities, and Sexual Propagation in (Amaryllidaceae).
Plants (Basel)
January 2025
Instituto de Biotecnología, Facultad de Ingeniería, Universidad Nacional de San Juan, Av. Libertador General San Martín 1109 (O), San Juan CP5400, Argentina.
, a recently described endemic species from southern Peru, belongs to the Amaryllidaceae family and is known for its diversity of alkaloids. Amaryllidoideae have been studied for their diverse biological activities, particularly for their properties in treating neurodegenerative diseases. This work examines the alkaloidal profile using GC-MS and UPLC-MS/MS of alkaloid-enriched extracts obtained from the leaves and bulbs of and their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes.
View Article and Find Full Text PDFResveratrol-Based Carbamates as Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, Computational Study and Biometal Complexation Capability.
Molecules
January 2025
Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Trg Marka Marulića 19, HR-10 000 Zagreb, Croatia.
Considering our previous experience in the design of new cholinesterase inhibitors, especially resveratrol analogs, in this research, the basic stilbene skeleton was used as a structural unit for new carbamates designed as potentially highly selective butyrylcholinesterase (BChE) inhibitors with excellent absorption, distribution, metabolism, excretion and toxicity ADMET properties. The inhibitory activity of newly prepared carbamates - was tested toward the enzymes acetylcholinesterase (AChE) and BChE. In the tested group of compounds, the leading inhibitors were and , which achieved excellent selective inhibitory activity for BChE with IC values of 0.
View Article and Find Full Text PDFCurcumin Solubility and Bioactivity Enhancement Through Amorphization with Tryptophan via Supercritical Fluid Technology.
Int J Mol Sci
January 2025
Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3 Str., 60-806 Poznan, Poland.
Curcumin, a compound known for its antioxidant and neuroprotective properties, faces challenges due to its low water solubility, which can limit its effectiveness. One effective method to address this issue is through amorphization. Incorporating curcumin into a polymeric matrix to form amorphous solid dispersions is a common approach.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!