Potent and Selective Monoamine Oxidase‐B Inhibitory Activity: Fluoro‐ vs. Trifluoromethyl‐4‐hydroxylated Chalcone Derivatives. Issue 8 (4th August 2016)

• Record Type: Journal Article
• Authors: Mathew, Bijo; Mathew, Githa Elizabeth; Uçar, Gülberk; Baysal, Ipek; Suresh, Jerad; Mathew, Sincy; Haridas, Abitha; Jayaprakash, Venkatesan
• Is Part Of: Chemistry & biodiversity. Volume 13:Issue 8(2016:Aug.)
• Page Start: 1046
• Page End: 1052
• Publication Date: 2016-08-04
• Subjects: Chalcone -- MAO‐A -- MAO‐B -- Molecular docking; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Biodiversity -- Periodicals; 572
• DOI: 10.1002/cbdv.201500367
• Languages: English
• ISSNs: 1612-1872

Abstract

Abstract : 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 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. Abstract : Potent and Selective Monoamine Oxidase‐B Inhibitory Activity: Fluoro‐ vs . Trifluoromethyl‐4‐hydroxylated Chalcone Derivatives B. Mathew*, G. E. Mathew, G. Uçar*, I. Baysal, J. Suresh, S. Mathew, A. Haridas, V. Jayaprakash