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Open AccessArticle

Exploring Biological Activity of 4-Oxo-4H-furo[2,3-h]chromene Derivatives as Potential Multi-Target-Directed Ligands Inhibiting Cholinesterases, β-Secretase, Cyclooxygenase-2, and Lipoxygenase-5/15

1
Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, Private Bag X06, Florida 1710, South Africa
2
Department of Life & Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa
*
Authors to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 736; https://doi.org/10.3390/biom9110736
Received: 23 October 2019 / Revised: 6 November 2019 / Accepted: 7 November 2019 / Published: 13 November 2019
(This article belongs to the Special Issue Cholinesterases in Alzheimer's Disease)
A series of 5-oxo-5H-furo[3,2-g]chromene-6-carbaldehydes and their hydrazone derivatives were evaluated as potential multi-target-directed ligands in vitro against cholinesterases, β-secretase, cyclooxygenase-2, and lipoxygenase-15 (LOX-15), as well as for free radical-scavenging activities. The most active compounds against LOX-15 were also evaluated for activity against the human lipoxygenase-5 (LOX-5). Kinetic studies against AChE, BChE, and β-secretase (BACE-1) were performed on 2-(3-fluorophenyl)- (3b) and 2-(4-chlorophenyl)-6-[(4-trifluoromethylphenyl)hydrazonomethyl]furo[3,2-h]chromen-5-one (3e) complemented with molecular docking (in silico) to determine plausible protein-ligand interactions on a molecular level. The docking studies revealed hydrogen and/or halogen bonding interactions between the strong electron-withdrawing fluorine atoms of the trifluoromethyl group with several residues of the enzyme targets, which are probably responsible for the observed increased biological activity of these hydrazone derivatives. The two compounds were found to moderately inhibit COX-2 and lipoxygenases (LOX-5 and LOX-15). Compounds 3b and 3e were also evaluated for cytotoxicity against the breast cancer MCF-7 cell line and Hek293-T cells. View Full-Text
Keywords: furochromones; cholinesterases; β-secretase; cyclooxygenase-2; lipoxygenases-5/15; anti-oxidant activity; cytotoxicity; molecular docking furochromones; cholinesterases; β-secretase; cyclooxygenase-2; lipoxygenases-5/15; anti-oxidant activity; cytotoxicity; molecular docking
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MDPI and ACS Style

Mphahlele, M.J.; Agbo, E.N.; Gildenhuys, S.; Setshedi, I.B. Exploring Biological Activity of 4-Oxo-4H-furo[2,3-h]chromene Derivatives as Potential Multi-Target-Directed Ligands Inhibiting Cholinesterases, β-Secretase, Cyclooxygenase-2, and Lipoxygenase-5/15. Biomolecules 2019, 9, 736.

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