Monoamine oxidase inhibitory activities of heterocyclic chalcones

Minders, Corné; Petzer, Jacobus P.; Petzer, Anél; Lourens, Anna C.U.

doi:10.1016/j.bmcl.2015.09.049

Cited by 57 publications

(40 citation statements)

References 51 publications

(51 reference statements)

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“…Prior studies revealed that the removal of the double bond system in chalcone leads to decreased activity in MAO inhibition . Additionally, heterocyclic substituents such as furan, chromene, thiophene, piperidine, quinoline, and indole in the chalcone scaffold lead to improved MAO inhibition . Recent reports have shown that chalcones are more potent inhibitors of MAO‐A than of MAO‐B.…”

Section: Figurementioning

confidence: 78%

Monoamine Oxidase Inhibitory Activity: Methyl‐ versus Chlorochalcone Derivatives

Mathew

Uçar

Mathew³

et al. 2016

ChemMedChem

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Numerous studies have shown that chalcones are promising scaffolds for the development of new monoamine oxidase-B (MAO-B) inhibitors. As a continuation of our ongoing research into the development of reversible human MAO-B (hMAO-B) inhibitors, two series of twenty chalcones containing electron-donating and electron-withdrawing substituents were synthesized. All compounds were found to be competitive, selective, and reversible inhibitors of hMAO-B except (2E)-1-(4-methylphenyl)-3-(4-nitrophenyl)prop-2-en-1-one (P7) and (2E)-1-(4-chlorophenyl)-3-(4-nitrophenyl)prop-2-en-1-one (P17), which were found to be selective inhibitors of hMAO-A. The most potent hMAO-B inhibitor, (2E)-1-(4-chlorophenyl)-3-(4-ethylphenyl)prop-2-en-1-one (P16), showed a K value of 0.11±0.01 μm. Molecular docking simulations were carried out to identify the hypothetical binding mode for the most potent compounds in the active sites of hMAO-A and B. The ability of the compounds to cross the blood-brain barrier was assessed by parallel artificial membrane permeability assay (PAMPA). Additionally, the most potent hMAO-B inhibitor P16 showed no toxicity in cultured hepatic cells at concentrations of 5 and 25 μm.

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Section: Figurementioning

confidence: 78%

Monoamine Oxidase Inhibitory Activity: Methyl‐ versus Chlorochalcone Derivatives

Mathew

Uçar

Mathew³

et al. 2016

ChemMedChem

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“…The privileged scaffold chalcone remained a fascination among researchers due to its simple chemistry, ease of synthesis, diversity of substituents and wide array of biological profiles . Numerous studies have shown that chalcones are considered as valid scaffold of MAO preferably MAO−B . The presence of hydroxy and methoxy groups or two hydroxy groups on the ortho and para position of the A aromatic moiety as well as a chlorine atom on the para position of the B ring of chalcones leads to potent MAO−B inhibitory action .…”

Section: Introductionmentioning

confidence: 99%

Characterization of Thienylchalcones as hMAO‐B Inhibitors: Synthesis, Biochemistry and Molecular Dynamics Studies

et al. 2017

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The design of selective, reversible and non‐toxic hMAO−B inhibitors has received increasing attention due to their perceived utility in targeting of neurological disorders like Alzheimer's and Parkinson's diseases. For this purpose, herein, we report the inhibitory studies on monoamine oxidase of a series of (2E)‐1‐(2, 5‐dichlorothiophen‐3‐yl)‐3‐(4‐substitutedphenyl) prop‐2‐en‐1‐ones (S1‐S9). All the compounds were found to be competitive, selective, and reversible inhibitors of hMAO−B except (2E)‐1‐(2, 4‐dichlorothiophen‐3‐yl)‐3‐(4‐nitrophenyl) prop‐2‐en‐1‐one (S6) which is found to be non‐selective MAO inhibitor. The potent hMAO−B inhibitor, (2E)‐1‐(2, 4‐dichlorothiophen‐3‐yl)‐3‐[4‐(dimethylamino) phenyl] prop‐2‐en‐1‐one (S4), showed a Ki value of 0.041 μM better than the standard drug, selegiline (hMAO−B with Ki= 0.302 μM). Moreover, S4, was nontoxic in cultured hepatic cells at 5 and 25 μM, with 94.44 and 88.00% viable cells, respectively. Molecular docking and molecular dynamics simulation studies were carried out using Autodock‐vina and Amber 14 to understand the molecular level interaction and energy relation of MAO isoforms with selective MAO−B inhibitor, S4.

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“…In this kind of compounds, the aromatic ring A is attached to the C=O group and the B ring to the β C‐atom of the three‐carbon unit. Chalcones are reported for their potential MAO inhibition by different groups . The most active chalcones were characterized by the presence of OH/MeO substituents either at ortho ‐positions with Cl‐atom or at para ‐position of the ring B .…”

Section: Introductionmentioning

confidence: 99%

Potent and Selective Monoamine Oxidase‐B Inhibitory Activity: Fluoro‐ vs. Trifluoromethyl‐4‐hydroxylated Chalcone Derivatives

Mathew

Mathew²,

Uçar³

et al. 2016

Chemistry & Biodiversity

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For various neurodegenerative disorders like Alzheimer's and Parkinson's diseases, selective and reversible MAO-B inhibitors have a great therapeutic value. In our previous study, we have shown that a series of methoxylated chalcones with F functional group exhibited high binding affinity toward human monoamine oxidase-B (hMAO-B). In continuation of our earlier study and to extend the understanding of the structure-activity relationships, a series of five new chalcones were studied for their inhibition of hMAO. The results demonstrated that these compounds are reversible and selective hMAO-B inhibitors with a competitive mode of inhibition. The most active compound, (2E)-1-(4-hydroxyphenyl)-3-[4-(trifluoromethyl)phenyl]prop-2-en-1-one, exhibited a Ki value of 0.33 ± 0.01 μm toward hMAO-B with a selectivity index of 26.36. A molecular docking study revealed that the presence of a H-bond network in hydroxylated chalcone with the N(5) atom of FAD is crucial for MAO-B selectivity and potency.

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Monoamine oxidase inhibitory activities of heterocyclic chalcones

Cited by 57 publications

References 51 publications

Monoamine Oxidase Inhibitory Activity: Methyl‐ versus Chlorochalcone Derivatives

Monoamine Oxidase Inhibitory Activity: Methyl‐ versus Chlorochalcone Derivatives

Characterization of Thienylchalcones as hMAO‐B Inhibitors: Synthesis, Biochemistry and Molecular Dynamics Studies

Potent and Selective Monoamine Oxidase‐B Inhibitory Activity: Fluoro‐ vs. Trifluoromethyl‐4‐hydroxylated Chalcone Derivatives

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