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Exploration of chlorinated thienyl chalcones: A new class of monoamine oxidase-B inhibitors
- Source :
- International Journal of Biological Macromolecules. 91:680-695
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 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 ± 0.02 μM and 16.84, respectively. All the compounds presented in the current study are completely non-toxic with 7488% viable cells to hepatic cells at 100 μM 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 .
- Subjects :
- 0301 basic medicine
Gene isoform
Chalcone
Monoamine Oxidase Inhibitors
Halogenation
Monoamine oxidase B inhibitors
Stereochemistry
Monoamine oxidase
Molecular Conformation
Molecular Dynamics Simulation
Ligands
Ring (chemistry)
01 natural sciences
Biochemistry
03 medical and health sciences
chemistry.chemical_compound
Chalcones
Molecular level
Structural Biology
Catalytic Domain
Humans
Monoamine Oxidase
Molecular Biology
Principal Component Analysis
Cell Death
010405 organic chemistry
Chemistry
MAO inhibitors
Hep G2 Cells
General Medicine
0104 chemical sciences
Isoenzymes
Molecular Docking Simulation
Kinetics
030104 developmental biology
Thermodynamics
Selectivity
Subjects
Details
- ISSN :
- 01418130
- Volume :
- 91
- Database :
- OpenAIRE
- Journal :
- International Journal of Biological Macromolecules
- Accession number :
- edsair.doi.dedup.....b9cf316becf090c4974b5571c2e2c5c9
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2016.05.110