Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds

doi:10.3390/molecules23020250

Paper

Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds

Published Jan 27, 2018 · A. Stefanachi, F. Leonetti, L. Pisani

Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry

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435

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3

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Abstract

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. In this review an overview of the most recent synthetic pathways leading to mono- and polyfunctionalized coumarins will be presented, along with the main biological pathways of their biosynthesis and metabolic transformations. The many existing and recent reviews in the field prompted us to make some drastic selections, and therefore, the review is focused on monoamine oxidase, cholinesterase, and aromatase inhibitors, and on multitarget coumarins acting on selected targets of neurodegenerative diseases.

Literature Review

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Study Snapshot

Coumarin is a versatile scaffold for medicinal chemists, enabling the design and development of selective enzyme inhibitors and multitarget ligands for neurodegenerative diseases.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds

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References

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

Compound 7f shows potential as a promising multi-target lead candidate for Alzheimer's disease treatment, with potent inhibitory activity for ChE and MAO-B, and no toxicity on PC12 neuroblastoma cells.

Synthesis and structure-activity relationship study of novel 3-heteroarylcoumarins based on pyridazine scaffold as selective MAO-B inhibitors.

Novel 3-heteroarylcoumarins based on pyridazine-coumarin show potent, selective, and reversible inhibition of MAO-B, with good pharmacokinetic profiles and no cytotoxic effects.

Coumarin derivatives: an updated patent review (2015-2016)

Synthetic coumarins and their derivatives show promising anticancer, antitumor, and anti-proliferative activities, warranting further clinical evaluation for potential therapeutic utility.

Evaluation of synthesized coumarin derivatives on aromatase inhibitory activity.

7-(pyridin-3-yl)coumarin and 7,7′-diethylamino-3,3′-biscoumarin are the most potent aromatase inhibitors, comparable to the existing CYP19 inhibitor exemestane.

Coumarins scaffolds as COX inhibitors.

Natural and synthetic coumarins show potential as COX-inhibitors, offering potential anti-inflammatory benefits without severe side effects.

A rational approach to elucidate human monoamine oxidase molecular selectivity

This study reveals that a stable H-bond interaction between 1 and Gln215 is crucial for ligand selectivity toward hMAO-A, while a water-mediated interaction may explain the observed hMAO-B selectivity of compound 2.

Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-Chromen-2-One Core: Structure-Based and Ligand-Based Derived Three-Dimensional Quantitative Structure-Activity Relationships Predictive Models

This study developed a 3-D QSAR model to select novel MAO B inhibitors, revealing six highly active and selective compounds, including D123 and D124, as potential anti-Parkinson's drugs.

Sonochemistry as a General Procedure for the Synthesis of Coumarins, Including Multigram Synthesis

Sonochemistry effectively synthesizes coumarins on a multigram scale, with higher yield, higher crystalline compound, and shorter reaction time compared to classical methods.

SnCl4 grafted on silica gel: an efficient catalyst for solvent-free synthesis of coumarins via the Pechmann condensation

SnCl4 grafted on silica gel effectively catalyzes solvent-free synthesis of substituted coumarins, offering high yields, simplicity, and green aspects.

Citations

Ethnopharmacology of Psychotria: Potential Use of P. malayana Jack Leaves as Antidiabetic Agent

Psychotria species, particularly P. malayana Jack leaves, show potential as antidiabetic agents with unique pharmacologically active compounds and safe toxicological profiles for drug development.

Coumarins: Chemical Synthesis, Properties and Applications

Coumarins show significant potential as new drug candidates due to their biocompatibility and diverse biological activities, including antimicrobial, anticancer, and antioxidant properties.

High-Pressure Extraction Techniques for Efficient Recovery of Flavonoids and Coumarins from Flower Seeds

High-pressure extraction methods, such as supercritical fluid extraction and pressurized liquid extraction, offer a greener, more efficient alternative to conventional methods for obtaining flavonoids and coumarins from flower seeds.

Structural characterization, theoretical, and antibacterial activity study of halogen-η3-allylpalladium(II) complexes incorporating 2-, 3- and 4-pyridyl-methylen-4-methylumbelliferone esters

Halogen-3-allylpalladium(II) complexes show potential antibacterial activity against both Gram-positive and Gram-negative bacteria.

Dioxolocoumarins: Bridging chemistry and pharmacology with multifunctional therapeutics

Dioxolocoumarin compounds (DCCs) show potential as anticancer agents, antimicrobial agents, and neuroprotective agents, offering diverse therapeutic benefits for various diseases.

A Review of Synthesis and Therapeutic Applications of Coumarin Derivatives

Coumarin derivatives show potential for drug discovery and development due to their low toxicity, natural abundance, and synthetic accessibility, with potential applications in antidiabetic, neuroprotective, and antituberculosis agents.

Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds

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References

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

Compound 7f shows potential as a promising multi-target lead candidate for Alzheimer's disease treatment, with potent inhibitory activity for ChE and MAO-B, and no toxicity on PC12 neuroblastoma cells.

Synthesis and structure-activity relationship study of novel 3-heteroarylcoumarins based on pyridazine scaffold as selective MAO-B inhibitors.

Novel 3-heteroarylcoumarins based on pyridazine-coumarin show potent, selective, and reversible inhibition of MAO-B, with good pharmacokinetic profiles and no cytotoxic effects.

Coumarin derivatives: an updated patent review (2015-2016)

Synthetic coumarins and their derivatives show promising anticancer, antitumor, and anti-proliferative activities, warranting further clinical evaluation for potential therapeutic utility.

Evaluation of synthesized coumarin derivatives on aromatase inhibitory activity.

7-(pyridin-3-yl)coumarin and 7,7′-diethylamino-3,3′-biscoumarin are the most potent aromatase inhibitors, comparable to the existing CYP19 inhibitor exemestane.

Coumarins scaffolds as COX inhibitors.

Natural and synthetic coumarins show potential as COX-inhibitors, offering potential anti-inflammatory benefits without severe side effects.

A rational approach to elucidate human monoamine oxidase molecular selectivity

This study reveals that a stable H-bond interaction between 1 and Gln215 is crucial for ligand selectivity toward hMAO-A, while a water-mediated interaction may explain the observed hMAO-B selectivity of compound 2.

Understanding the Molecular Determinant of Reversible Human Monoamine Oxidase B Inhibitors Containing 2H-Chromen-2-One Core: Structure-Based and Ligand-Based Derived Three-Dimensional Quantitative Structure-Activity Relationships Predictive Models

This study developed a 3-D QSAR model to select novel MAO B inhibitors, revealing six highly active and selective compounds, including D123 and D124, as potential anti-Parkinson's drugs.

Sonochemistry as a General Procedure for the Synthesis of Coumarins­, Including Multigram Synthesis

Sonochemistry effectively synthesizes coumarins on a multigram scale, with higher yield, higher crystalline compound, and shorter reaction time compared to classical methods.

SnCl4 grafted on silica gel: an efficient catalyst for solvent-free synthesis of coumarins via the Pechmann condensation

SnCl4 grafted on silica gel effectively catalyzes solvent-free synthesis of substituted coumarins, offering high yields, simplicity, and green aspects.

Citations

Ethnopharmacology of Psychotria: Potential Use of P. malayana Jack Leaves as Antidiabetic Agent

Psychotria species, particularly P. malayana Jack leaves, show potential as antidiabetic agents with unique pharmacologically active compounds and safe toxicological profiles for drug development.

Coumarins: Chemical Synthesis, Properties and Applications

Coumarins show significant potential as new drug candidates due to their biocompatibility and diverse biological activities, including antimicrobial, anticancer, and antioxidant properties.

High-Pressure Extraction Techniques for Efficient Recovery of Flavonoids and Coumarins from Flower Seeds

High-pressure extraction methods, such as supercritical fluid extraction and pressurized liquid extraction, offer a greener, more efficient alternative to conventional methods for obtaining flavonoids and coumarins from flower seeds.

Structural characterization, theoretical, and antibacterial activity study of halogen-η3-allylpalladium(II) complexes incorporating 2-, 3- and 4-pyridyl-methylen-4-methylumbelliferone esters

Halogen-3-allylpalladium(II) complexes show potential antibacterial activity against both Gram-positive and Gram-negative bacteria.

Dioxolocoumarins: Bridging chemistry and pharmacology with multifunctional therapeutics

Dioxolocoumarin compounds (DCCs) show potential as anticancer agents, antimicrobial agents, and neuroprotective agents, offering diverse therapeutic benefits for various diseases.

A Review of Synthesis and Therapeutic Applications of Coumarin Derivatives

Coumarin derivatives show potential for drug discovery and development due to their low toxicity, natural abundance, and synthetic accessibility, with potential applications in antidiabetic, neuroprotective, and antituberculosis agents.

Sonochemistry as a General Procedure for the Synthesis of Coumarins, Including Multigram Synthesis