Synthesis, characterization, crystal structure and evaluation of four carbazole-coumarin hybrids as multifunctional agents for the treatment of Alzheimer’s disease

Abstract Coupling of two distinct pharmacophores, carbazole and coumarin, endowed with different biological properties, afforded four hybrid compounds. The structures of the carbazole-coumarin hybrids were characterized by FT-IR, NMR, HRMS and single-crystal X-ray diffraction studies. All of these compounds exhibited significant acetylcholinesterase inhibitory activities. Among them, compound 4-((5-(9H-carbazol-9-yl)pentyl)oxy)-2H-chromen-2-one (3d) exhibited the best inhibition activity with IC50 of 3.75 μM for acetylcholinesterase from electric eel and 70.51 μM for human recombinant acetylcholinesterase. Moreover, the compound 7-(3-(9H-carbazol-9-yl propoxy)-4-methyl-2H-chromen-2-one (3a) had the best antioxidant activity. The docking studies demonstrated that compound 3d could interact with both the catalytic active site and the peripheral anionic site of acetylcholinesterase. These attributes imply carbazole-coumarin hybrids as multifunctional agents for the Alzheimer’s disease treatment.

• Publication year

  2020

• Venue

  Journal of Molecular Structure

• Publication date

  2020-06-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.molstruc.2020.127897
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Rational approaches, design strategies, structure activity relationship and mechanistic insights for therapeutic coumarin hybrids.

  2019cited by this paper
• Novel tacrine-coumarin hybrids linked to 1,2,3-triazole as anti-Alzheimer's compounds: In vitro and in vivo biological evaluation and docking study.

  2019cited by this paper
• Overview of novel multifunctional agents based on conjugates of γ-carbolines, carbazoles, tetrahydrocarbazoles, phenothiazines, and aminoadamantanes for treatment of Alzheimer's disease.

  2019cited by this paper
• Design, synthesis and biological evaluation of hydroxypyridinone-coumarin hybrids as multimodal monoamine oxidase B inhibitors and iron chelates against Alzheimer's disease.

  2019cited by this paper
• Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation.

  2018cited by this paper
• Design, synthesis and biological evaluation of new coumarin-dithiocarbamate hybrids as multifunctional agents for the treatment of Alzheimer's disease.

  2018cited by this paper
• Molecular docking studies of coumarin hybrids as potential acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A/B and β-amyloid inhibitors for Alzheimer’s disease

  2018cited by this paper
• Development of coumarin–benzofuran hybrids as versatile multitargeted compounds for the treatment of Alzheimer’s Disease

  2018cited by this paper
• Design, synthesis and biological evaluation of novel coumarin-N-benzyl pyridinium hybrids as multi-target agents for the treatment of Alzheimer's disease.

  2017cited by this paper
• Design, synthesis and biological evaluation of phthalimide-alkylamine derivatives as balanced multifunctional cholinesterase and monoamine oxidase-B inhibitors for the treatment of Alzheimer's disease.

  2017cited by this paper
• Design, synthesis, biological evaluation, and molecular modeling studies of chalcone-rivastigmine hybrids as cholinesterase inhibitors.

  2017cited by this paper
• Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-β-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease.

  2017cited by this paper
• Design, synthesis, and evaluation of salicyladimine derivatives as multitarget-directed ligands against Alzheimer's disease.

  2017cited by this paper
• 2016 Alzheimer's disease facts and figures

  2016cited by this paper
• Design, synthesis and biological evaluation of novel donepezil-coumarin hybrids as multi-target agents for the treatment of Alzheimer's disease.

  2016cited by this paper
• Ferulic acid-carbazole hybrid compounds: Combination of cholinesterase inhibition, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents.

  2016cited by this paper
• Coumarins as cholinesterase inhibitors: A review.

  2016cited by this paper
• Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors.

  2015cited by this paper
• Multi-target tacrine-coumarin hybrids: cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease.

  2015cited by this paper
• DT‐01‐04: The efficacy of RVT‐101, a 5‐ht6 receptor antagonist, as an adjunct to donepezil in adults with mild‐to‐moderate Alzheimer's disease: Completer analysis of a phase 2b study

  2015cited by this paper
• Multifunctional tacrine-trolox hybrids for the treatment of Alzheimer's disease with cholinergic, antioxidant, neuroprotective and hepatoprotective properties.

  2015cited by this paper
• Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives.

  2014cited by this paper
• Oxidative stress in Alzheimer's disease: are we connecting the dots?

  2014cited by this paper
• Design, synthesis and biological evaluation of D-ring opened galantamine analogs as multifunctional anti-Alzheimer agents.

  2014cited by this paper
• Indolinone-based acetylcholinesterase inhibitors: synthesis, biological activity and molecular modeling.

  2014cited by this paper
• Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer's disease.

  2014cited by this paper
• Syntheses of coumarin-tacrine hybrids as dual-site acetylcholinesterase inhibitors and their activity against butylcholinesterase, Aβ aggregation, and β-secretase.

  2014cited by this paper
• Synthesis and biological evaluation of novel tacrine derivatives and tacrine-coumarin hybrids as cholinesterase inhibitors.

  2014cited by this paper
• Novel coumarin-3-carboxamides bearing N-benzylpiperidine moiety as potent acetylcholinesterase inhibitors.

  2013cited by this paper
• Coumarin-based inhibitors of Bacillus anthracis and Staphylococcus aureus replicative DNA helicase: chemical optimization, biological evaluation, and antibacterial activities.

  2012cited by this paper
• Inhibition of beta-amyloid peptide aggregation by multifunctional carbazole-based fluorophores.

  2012cited by this paper
• Design, synthesis, and acetylcholinesterase inhibitory activity of novel coumarin analogues.

  2008cited by this paper
• Mercury CSD 2.0 – new features for the visualization and investigation of crystal structures

  2008cited by this paper
• Free-radical-scavenging effect of carbazole derivatives on AAPH-induced hemolysis of human erythrocytes.

  2007cited by this paper
• Donepezil for dementia due to Alzheimer's disease.

  2006cited by this paper
• Galantamine for Alzheimer's disease.

  2004cited by this paper
• Galantamine for dementia due to Alzheimer's disease

  2002cited by this paper
• SADABS, Program for Empirical Absorption Correction of Area Detector Data

  1996cited by this paper
• A new and rapid colorimetric determination of acetylcholinesterase activity.

  1961cited by this paper

• NOVEL HETEROCYCLIC HYBRIDS AS PROMISING SCAFFOLD FOR THE MANAGEMENT OF ALZHEIMER’S DISEASE

  2025cites this paper
• Analysis of skeletal diversity of multi-target directed ligands (MTDLs) targeting Alzheimer's disease.

  2025cites this paper
• Computational and Experimental Insights into the Anticancer as Well as Antimicrobial Activity of Coumarin‐1,2,3‐Triazole Derivatives: A Study Based on DFT, Docking, ADME, and In Vitro Assays

  2025cites this paper
• Sustainable Strategies for Carbazole Synthesis: A Green Chemistry Perspective

  2025cites this paper
• COMPARATIVE MOLECULAR DOCKING STUDIES OF 7-HYDROXY COUMARIN DERIVATIVES

  2025cites this paper
• Design, synthesis and anticholinesterase activity of coumarin-1,3,5-triazine derivatives

  2025cites this paper
• Design of Multi-Target drugs of HDACs and other Anti-Alzheimer related Targets: Current strategies and future prospects in Alzheimer's diseases therapy.

  2024cites this paper
• Multi-target directed ligands inspired natural products as an effective approach for the treatment of complex chronic health disorders.

  2024cites this paper
• Naturally Inspired Coumarin Derivatives in Alzheimer’s Disease Drug Discovery: Latest Advances and Current Challenges

  2024cites this paper
• Design, Synthesis and Anticholinesterase Activity of Coumarin‐1,3,5‐triazine Derivatives

  2024cites this paper
• A Review on Recent Approaches on Molecular Docking Studies of Novel Compounds Targeting Acetylcholinesterase in Alzheimer Disease

  2023cites this paper
• Synthesis, Characterization, Crystal Structure, and cholinesterase Inhibitory Activity of 2-Phenylthiazole Derivatives

  2023cites this paper
• Synthesis and Acetylcholinesterase Inhibitory Evaluation of Coumarin‐Linked Carbazole Derivatives

  2023cites this paper
• Coumarin Derivatives: Mechanistic Insights and Promising Applications as Potential Alzheimer's Disease (AD) Therapeutic Agents

  2023cites this paper
• A series of 1,2,3-triazole compounds: Synthesis, characterization, and investigation of the cholinesterase inhibitory properties via in vitro and in silico studies

  2022cites this paper
• Design, synthesis, characterization and evaluation of 1,3,5-triazine-benzimidazole hybrids as multifunctional acetylcholinesterases inhibitors

  2022cites this paper
• Therapeutic potential of 4-substituted coumarins: A conspectus

  2022cites this paper
• Synthesis, Biological Evaluation and Molecular Modeling Studies of Novel Carbazole-Benzylpiperazine Hybrids as Acetylcholinesterase and Butyrylcholinesterase Inhibitors

  2022cites this paper
• Synthesis, characterization, crystal structure and biological evaluation of 1,3,5-triazine-quinoline derivatives as butyrylcholinesterase inhibitors

  2022cites this paper
• Investigation of biological activities of various 1,2,3‐triazole compounds: Their effects on cholinesterase enzymes, determination of antioxidant capacity and antimicrobial activity

  2022cites this paper
• Trending Topics on Coumarin and Its Derivatives in 2020

  2021cites this paper
• Novel series of triazole containing coumarin and isatin based hybrid molecules as acetylcholinesterase inhibitors

  2021cites this paper
• Coumarin linked heterocyclic hybrids: A promising approach to develop multi target drugs for Alzheimer's disease

  2021cites this paper
• Design, multistep synthesis and in-vitro antimicrobial and antioxidant screening of coumarin clubbed chalcone hybrids through molecular hybridization approach

  2021cites this paper
• Nucleophilic reactions with the novel condensation product derived from 3-formylchromone and 4-hydroxycoumarin

  2021cites this paper
• Design, synthesis and biological evaluation of new carbazole-coumarin hybrids as dual binding site inhibitors of acetylcholinesterase

  2021cites this paper
• Design, synthesis and biological activity evaluation of novel carbazole-benzylpiperidine hybrids as potential anti Alzheimer agents

  2020cites this paper
• Synthesis of carbazole based α-aminophosphonate derivatives: design, molecular docking and in vitro cholinesterase activity

  2020cites this paper
• Synthesis of novel 4-methylthiocoumarin and comparison with conventional coumarin derivative as a multi-target-directed ligand in Alzheimer’s disease

  2020cites this paper
• An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

  2020cites this paper