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Coumarin-Chalcone Hybrids as Inhibitors of MAO-B: Biological Activity and In Silico Studies.

ABSTRACT: Fourteen coumarin-derived compounds modified at the C3 carbon of coumarin with an α,β-unsaturated ketone were synthesized. These compounds may be designated as chalcocoumarins (3-cinnamoyl-2H-chromen-2-ones). Both chalcones and coumarins are recognized scaffolds in medicinal chemistry, showing diverse biological and pharmacological properties among which neuroprotective activities and multiple enzyme inhibition, including mitochondrial enzyme systems, stand out. The evaluation of monoamine oxidase B (MAO-B) inhibitors has aroused considerable interest as therapeutic agents for neurodegenerative diseases such as Parkinson's. Of the fourteen chalcocumarins evaluated here against MAO-B, ChC4 showed the strongest activity in vitro, with IC₅₀ = 0.76 ± 0.08 µM. Computational docking, molecular dynamics and MM/GBSA studies, confirm that ChC4 binds very stably to the active rMAO-B site, explaining the experimental inhibition data.

SUBMITTER: Moya-Alvarado G

PROVIDER: S-EPMC8122463 | biostudies-literature |

REPOSITORIES: biostudies-literature

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| S-EPMC9271751 | biostudies-literature

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| S-EPMC7470021 | biostudies-literature

Design, synthesis, in vitro, and in silico biological evaluations of coumarin-indole hybrids as new anti-α-glucosidase agents.

Project description:BackgroundA series of coumarin-indole hybrids was synthesized as the new α-glucosidase inhibitors. The title hybrids were considered as α-glucosidase inhibitors because had two active pharmacophores against α-glucosidase: coumarin and indole.MethodsThe thirteen various derivatives 4a-m were synthesized, purified, and fully characterized. These compounds were evaluated against α-glucosidase in vitro and in silico. In silico pharmacokinetic studies of the most potent compounds were also performed.ResultsMost of the title compounds exhibited high anti-α-glucosidase activity in comparison to standard drug acarbose. In particular, the phenoxy derivative 4d namely 3-((1H-indol-3-yl)(3-phenoxyphenyl)methyl)-4-hydroxy-2H-chromen-2-one showed promising activity. This compound is a competitive inhibitor against α-glucosidase and showed the lowest binding energy at the α-glucosidase active site in comparison to other potent synthesized compounds and acarbose.ConclusionCompound 4d can be a lead compound for further structural development to obtain effective and potent α-glucosidase inhibitors.

| S-EPMC9635080 | biostudies-literature

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