Anacardic acid derived salicylates are inhibitors or activators of lipoxygenases

Rosalina Wisastra; Massimo Ghizzoni; Andre Boltjes; Hidde J. Haisma; Frank J. Dekker

doi:10.1016/j.bmc.2012.06.019

Anacardic acid derived salicylates are inhibitors or activators of lipoxygenases

Rosalina Wisastra, Massimo Ghizzoni, Andre Boltjes, Hidde J. Haisma, Frank J. Dekker^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

27 Citations (Scopus)

Abstract

Lipoxygenases catalyze the oxidation of unsaturated fatty acids, such as linoleic acid, which play a crucial role in inflammatory responses. Selective inhibitors may provide a new therapeutic approach for inflammatory diseases. In this study, we describe the identification of a novel soybean lipoxygenase-1 (SLO-1) inhibitor and a potato 5-lipoxygenase (5-LOX) activator from a screening of a focused compound collection around the natural product anacardic acid. The natural product anacardic acid inhibits SLO-1 with an IC50 of 52 mu M, whereas the inhibitory potency of the novel mixed type inhibitor 23 is fivefold enhanced. In addition, another derivative (21) caused non-essential activation of potato 5-LOX. This suggests the presence of an allosteric binding site that regulates the lipoxygenase activity. (C) 2012 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	5027-5032
Number of pages	6
Journal	Bioorganic & Medicinal Chemistry
Volume	20
Issue number	16
DOIs	https://doi.org/10.1016/j.bmc.2012.06.019
Publication status	Published - 15-Aug-2012

Keywords

Anacardic acid
Soybean lipoxygenase-1
Potato 5-LOX
Enzyme inhibition
Enzyme activation
STEADY-STATE KINETICS
SOYBEAN LIPOXYGENASE-1
LINOLEIC-ACID
FATTY-ACIDS
5-LIPOXYGENASE
INFLAMMATION
ATHEROSCLEROSIS
15-LIPOXYGENASE
OXYGENATION
POTENT

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Anacardic acid derived salicylates are inhibitors or activators of lipoxygenases
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title = "Anacardic acid derived salicylates are inhibitors or activators of lipoxygenases",

abstract = "Lipoxygenases catalyze the oxidation of unsaturated fatty acids, such as linoleic acid, which play a crucial role in inflammatory responses. Selective inhibitors may provide a new therapeutic approach for inflammatory diseases. In this study, we describe the identification of a novel soybean lipoxygenase-1 (SLO-1) inhibitor and a potato 5-lipoxygenase (5-LOX) activator from a screening of a focused compound collection around the natural product anacardic acid. The natural product anacardic acid inhibits SLO-1 with an IC50 of 52 mu M, whereas the inhibitory potency of the novel mixed type inhibitor 23 is fivefold enhanced. In addition, another derivative (21) caused non-essential activation of potato 5-LOX. This suggests the presence of an allosteric binding site that regulates the lipoxygenase activity. (C) 2012 Elsevier Ltd. All rights reserved.",

keywords = "Anacardic acid, Soybean lipoxygenase-1, Potato 5-LOX, Enzyme inhibition, Enzyme activation, STEADY-STATE KINETICS, SOYBEAN LIPOXYGENASE-1, LINOLEIC-ACID, FATTY-ACIDS, 5-LIPOXYGENASE, INFLAMMATION, ATHEROSCLEROSIS, 15-LIPOXYGENASE, OXYGENATION, POTENT",

author = "Rosalina Wisastra and Massimo Ghizzoni and Andre Boltjes and Haisma, {Hidde J.} and Dekker, {Frank J.}",

year = "2012",

month = aug,

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doi = "10.1016/j.bmc.2012.06.019",

language = "English",

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journal = "Bioorganic & Medicinal Chemistry",

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number = "16",

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T1 - Anacardic acid derived salicylates are inhibitors or activators of lipoxygenases

AU - Wisastra, Rosalina

AU - Ghizzoni, Massimo

AU - Boltjes, Andre

AU - Haisma, Hidde J.

AU - Dekker, Frank J.

PY - 2012/8/15

Y1 - 2012/8/15

N2 - Lipoxygenases catalyze the oxidation of unsaturated fatty acids, such as linoleic acid, which play a crucial role in inflammatory responses. Selective inhibitors may provide a new therapeutic approach for inflammatory diseases. In this study, we describe the identification of a novel soybean lipoxygenase-1 (SLO-1) inhibitor and a potato 5-lipoxygenase (5-LOX) activator from a screening of a focused compound collection around the natural product anacardic acid. The natural product anacardic acid inhibits SLO-1 with an IC50 of 52 mu M, whereas the inhibitory potency of the novel mixed type inhibitor 23 is fivefold enhanced. In addition, another derivative (21) caused non-essential activation of potato 5-LOX. This suggests the presence of an allosteric binding site that regulates the lipoxygenase activity. (C) 2012 Elsevier Ltd. All rights reserved.

AB - Lipoxygenases catalyze the oxidation of unsaturated fatty acids, such as linoleic acid, which play a crucial role in inflammatory responses. Selective inhibitors may provide a new therapeutic approach for inflammatory diseases. In this study, we describe the identification of a novel soybean lipoxygenase-1 (SLO-1) inhibitor and a potato 5-lipoxygenase (5-LOX) activator from a screening of a focused compound collection around the natural product anacardic acid. The natural product anacardic acid inhibits SLO-1 with an IC50 of 52 mu M, whereas the inhibitory potency of the novel mixed type inhibitor 23 is fivefold enhanced. In addition, another derivative (21) caused non-essential activation of potato 5-LOX. This suggests the presence of an allosteric binding site that regulates the lipoxygenase activity. (C) 2012 Elsevier Ltd. All rights reserved.

KW - Anacardic acid

KW - Soybean lipoxygenase-1

KW - Potato 5-LOX

KW - Enzyme inhibition

KW - Enzyme activation

KW - STEADY-STATE KINETICS

KW - SOYBEAN LIPOXYGENASE-1

KW - LINOLEIC-ACID

KW - FATTY-ACIDS

KW - 5-LIPOXYGENASE

KW - INFLAMMATION

KW - ATHEROSCLEROSIS

KW - 15-LIPOXYGENASE

KW - OXYGENATION

KW - POTENT

U2 - 10.1016/j.bmc.2012.06.019

DO - 10.1016/j.bmc.2012.06.019

M3 - Article

C2 - 22789707

SN - 0968-0896

VL - 20

SP - 5027

EP - 5032

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 16

ER -

Anacardic acid derived salicylates are inhibitors or activators of lipoxygenases

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Keywords

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