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Potent and Selective Monoamine Oxidase‐B Inhibitory Activity: Fluoro‐ vs . Trifluoromethyl‐4‐hydroxylated Chalcone Derivatives
Author(s) -
Mathew Bijo,
Mathew Githa Elizabeth,
Uçar Gülberk,
Baysal Ipek,
Suresh Jerad,
Mathew Sincy,
Haridas Abitha,
Jayaprakash Venkatesan
Publication year - 2016
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201500367
Subject(s) - chemistry , chalcone , monoamine oxidase , trifluoromethyl , stereochemistry , selectivity , monoamine oxidase b , monoamine neurotransmitter , potency , enzyme , biochemistry , in vitro , organic chemistry , receptor , serotonin , alkyl , catalysis
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, (2 E )‐1‐(4‐hydroxyphenyl)‐3‐[4‐(trifluoromethyl)phenyl]prop‐2‐en‐1‐one, exhibited a K i value of 0.33 ± 0.01 μ m 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.