title: Monoamine oxidase inhibitory activity of 2-aryl-4H-chromen-4-ones.
abstract: A series of twenty 2-aryl-4H-chromen-4-one (flavones) derivatives (3a-3s) were synthesized and tested for hMAO inhibitory activity. Fifteen compounds (3a, 3c, 3e-3h, 3j-3p, 3r, 3s) were found to be selective towards MAO-B, while 3d was selective towards MAO-A, and 3b, 3i and 3q were non-selective. Experimental Selectivity Index for MAO-B ranges from 2.0 (3g, 3p) to 30.0 (3j). Compound 3j, which is carrying 3,4-di-OMeC6H3 groups at R position on the molecule, was found to be potent MAO-B inhibitor amongst the fifteen with Ki value for MAO-B of 0.16±0.01 μM comparable to that of standard drug, Selegiline (Ki for MAO-B is 0.16±0.01 μM). Compound 3j also appeared as the most selective MAO-B inhibitor according to its best selectivity index (30.0), which is comparable to that of Selegiline (SIMAO-B=35.0). Molecular docking and molecular dynamics simulation studies were carried out using Autodock-4.0 and Amber12 to understand the molecular level interaction and energy relation of MAO isoforms with selective inhibitors (3d and 3j). Simulation results are in good agreement with the experimental results. Leads identified may further be explored to develop potent isoform specific inhibitors of MAO.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835 215, India.
authors.forename: Badavath Vishnu
authors.initials: BV
authors.lastname: Nayak
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye 06100, Ankara, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Ciftci-Yabanoglu
authors.affiliation: School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa.
authors.forename: Soumendranath
authors.initials: S
authors.lastname: Bhakat
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835 215, India.
authors.forename: Ajay Kumar
authors.initials: AK
authors.lastname: Timiri
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835 215, India.
authors.forename: Barij N
authors.initials: BN
authors.lastname: Sinha
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Sıhhiye 06100, Ankara, Turkey. Electronic address: gulberk@hacettepe.edu.tr.
authors.forename: G
authors.initials: G
authors.lastname: Ucar
authors.affiliation: School of Health Sciences, University of KwaZulu-Natal, Westville, Durban 4001, South Africa.
authors.forename: Mahmoud E S
authors.initials: ME
authors.lastname: Soliman
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835 215, India; Valens Pharma Services, Regus Citi Centre, Level 6, Chennai Citi Centre, 10/11, Dr. Radhakrishnan Salai, Chennai, Tamil Nadu 600 004, India. Electronic address: venkatesanj@bitmesra.ac.in.
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Jayaprakash
mesh_terms: D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D007700:Kinetics; D062105:Molecular Docking Simulation; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D001578:Benzopyrans; D008996:Monoamine Oxidase Inhibitors
keywords: Enzyme inhibitors; Flavones; Human monoamine oxidase; Molecular docking; Molecular dynamics