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Exploration of chlorinated thienyl chalcones: A new class of monoamine oxidase-B inhibitors

Authors :
Monu Joy
Mahmoud E. S. Soliman
Githa Elizabeth Mathew
Bijo Mathew
Ipek Baysal
Adebayo A. Adeniyi
Abitha Haridas
Baskar Lakshmanan
Gulberk Ucar
Venkatesan Jayaprakash
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 74⿿88% 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 .

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