O-prenylated 3-carboxycoumarins as a novel class of 15-LOX-1 inhibitors

Jabbari, A. and Mousavian, M. and Seyedi, S. M. and Bakavoli, M. and Sadeghian, H. (2017) O-prenylated 3-carboxycoumarins as a novel class of 15-LOX-1 inhibitors. PLoS ONE, 12 (2).

[img] Text
pone.0171789.pdf

Download (1MB)

Abstract

Allyloxy, Isopentenyloxy, geranyloxy and farnesyloxy derivatives of 3-carboxycoumarin, at position 5, 6, 7, and 8, were synthesized and their inhibitory potency against human 15- lipoxygenase-1 (human 15-LOX-1) were determined. Among the synthetic coumarins, Oallyl and O-isopentenyl derivatives demonstrated no considerable lipoxygenase inhibition while O-geranyl and O-farnesyl derivatives demonstrated potent inhibitory activity. 5-farnesyloxy- 3-carboxycoumarin demonstrated the most potent inhibitory activity by IC50 = 0.74 μM while 6-farnesyloxy-3-carboxycoumarin was the weakest inhibitor among farnesyl analogs (IC50 = 10.4 μM). Bonding affinity of the designed molecular structures toward 15- LOX-1 3D structure complexed with RS75091, as potent 15-LOX-1 inhibitor, was studied by utilizing docking analysis. There was a direct relationship between lipoxygenase inhibitory potency and prenyl length chain. The ability of the prenyl portion to fill the lipophilic pocket which is formed by Ile663, Ala404, Arg403, Ile400, Ile173 and Phe167 side chains can explain the observed relationship. Similarity rate between the docked models and complexed form of RS75091, from point of view of configuration and conformation, could explain inhibitory potency variation between each prenyloxy substitution of 3-carboxycoumarins. © 2017 Jabbari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Item Type: Article
Additional Information: Cited By :3 Export Date: 16 February 2020 CODEN: POLNC
Uncontrolled Keywords: 15 lipoxygenase 1 5 (3 methylbut 2 enyloxy) 2 oxo 2h chromene 3 carboxylic acid 5 (3,7 dimethylocta 2,6 dienyloxy) 2 oxo 2h chromene 3 carboxylic acid 5 (3,7,11 trimethyldodeca 2,6,10 trienyloxy) 2 oxo 2h chromene 3 carboxylic acid 5 (allyloxy) 2 oxo 2h chromene 3 carboxylic acid 6 (3 methylbut 2 enyloxy) 2 oxo 2h chromene 3 carboxylic acid 6 (3,7,11 trimethyldodeca 2,6,10 trienyloxy) 2 oxo 2h chromene 3 carboxylic acid 6 (allyloxy) 2 oxo 2h chromene 3 carboxylic acid 7 (3 methylbut 2 enyloxy) 2 oxo 2h chromene 3 carboxylic acid 7 (3,7 dimethylocta 2,6 dienyloxy) 2 oxo 2h chromene 3 carboxylic acid 7 (3,7,11 trimethyldodeca 2,6,10 trienyloxy) 2 oxo 2h chromene 3 carboxylic acid 7 (allyloxy) 2 oxo 2h chromene 3 carboxylic acid 8 (3 methylbut 2 enyloxy) 2 oxo 2h chromene 3 carboxylic acid 8 (3,7 dimethylocta 2,6 dienyloxy) 2 oxo 2h chromene 3 carboxylic acid 8 (3,7,11 trimethyldodeca 2,6,10 trienyloxy) 2 oxo 2h chromene 3 carboxylic acid 8 (allyloxy) 2 oxo 2h chromene 3 carboxylic acid arachidonate 15 lipoxygenase coumarin derivative ethyl 6 (3,7 dimethylocta 2,6 dienyloxy) 2 oxo 2h chromene 3 carboxylic acid lipoxygenase inhibitor unclassified drug protein binding Article binding affinity chemical structure drug potency drug structure drug synthesis enzyme inhibition IC50 molecular docking structure activity relation binding site chemistry classification human metabolism molecular model prenylation Arachidonate 15-Lipoxygenase Binding Sites Coumarins Humans Lipoxygenase Inhibitors Models, Molecular Molecular Docking Simulation Molecular Structure Structure-Activity Relationship
Subjects: QU Biochemistry
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib3 lib3
Date Deposited: 27 Apr 2020 08:29
Last Modified: 27 Apr 2020 08:29
URI: http://eprints.mums.ac.ir/id/eprint/16866

Actions (login required)

View Item View Item