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Publication Type : Journal Article
Publisher : Int J Biol Macromol
Source : Int J Biol Macromol, Volume 91, p.680-95 (2016)
Keywords : Catalytic Domain, Cell death, Chalcones, Halogenation, Hep G2 Cells, Humans, Isoenzymes, kinetics, Ligands, Molecular Conformation, Molecular Docking Simulation, Molecular Dynamics Simulation, Monoamine oxidase, Monoamine Oxidase Inhibitors, Principal component analysis, thermodynamics
Campus : Kochi
School : School of Pharmacy
Department : Pharmaceutical Chemistry & Analysis
Year : 2016
Abstract : Chalcone has been reported to be a valid scaffold for the design of monoamine oxidase (MAO) inhibitors. This scenario has amplified the momentum for the discovery of heteroaryl based chalcone MAO inhibitors. In the present study, we have synthesized a series of eleven chlorinated thienyl chalcone derivatives substituted with a different functional groups at the para- position on the ring B and investigated for their ability to inhibit human MAO-A and -B. With the exception of compound (2E)-1-(4-chlorocyclopenta-1,3-dien-1-yl)-3-(4-nitrophenyl)prop-2-en-1-one (TC7), which was a selective MAO-A inhibitor, all the other derivatives inhibited hMAO-B potently and selectively with competitive mode of inhibition. The most potent compound (2E)-1-(4-chlorocyclopenta-1,3-dien-1-yl)-3-(4-ethylphenyl)prop-2-en-1-one (TC6) was found to be the best activity and higher selectivity towards hMAO-B with Ki and SI values of 0.31±0.02μM and 16.84, respectively. All the compounds presented in the current study are completely non-toxic with 74-88% viable cells to hepatic cells at 100μM concentration. Molecular docking and molecular dynamics simulation studies were carried out using Autodock-4.2 and Amber 14 to understand the molecular level interaction and energy relation of MAO isoforms with selective MAO-B inhibitor TC6.
Cite this Research Publication : Bijo Mathew, Haridas, A., Ucar, G., Baysal, I., Adeniyi, A. A., Soliman, M. E. S., Joy, M., Mathew, G. Elizabeth, Lakshmanan, B., and Jayaprakash, V., “Exploration of chlorinated thienyl chalcones: A new class of monoamine oxidase-B inhibitors.”, Int J Biol Macromol, vol. 91, pp. 680-95, 2016.