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Replacement of an Indole Scaffold Targeting Human 15‐Lipoxygenase‐1 Using Combinatorial Chemistry
Human 15‐lipoxygenase‐1 (15‐LOX‐1) belongs to the class of lipoxygenases, which catalyze oxygenation of polyunsaturated fatty acids, such as arachidonic and linoleic acid. Recent studies have shown that 15‐LOX‐1 plays an important role in physiological processes linked to several diseases such as ai...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563716/ https://www.ncbi.nlm.nih.gov/pubmed/31231138 http://dx.doi.org/10.1002/hlca.201900040 |
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author | Prismawan, Deka van der Vlag, Ramon Guo, Hao Dekker, Frank J. Hirsch, Anna K. H. |
author_facet | Prismawan, Deka van der Vlag, Ramon Guo, Hao Dekker, Frank J. Hirsch, Anna K. H. |
author_sort | Prismawan, Deka |
collection | PubMed |
description | Human 15‐lipoxygenase‐1 (15‐LOX‐1) belongs to the class of lipoxygenases, which catalyze oxygenation of polyunsaturated fatty acids, such as arachidonic and linoleic acid. Recent studies have shown that 15‐LOX‐1 plays an important role in physiological processes linked to several diseases such as airway inflammation disease, coronary artery disease, and several types of cancer such as rectal, colon, breast and prostate cancer. In this study, we aimed to extend the structural diversity of 15‐LOX‐1 inhibitors, starting from the recently identified indolyl core. In order to find new scaffolds, we employed a combinatorial approach using various aromatic aldehydes and an aliphatic hydrazide tail. This scaffold‐hopping study resulted in the identification of the 3‐pyridylring as a suitable replacement of the indolyl core with an inhibitory activity in the micromolar range (IC (50)=16±6 μm) and a rapid and efficient structure–activity relationship investigation. |
format | Online Article Text |
id | pubmed-6563716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65637162019-06-20 Replacement of an Indole Scaffold Targeting Human 15‐Lipoxygenase‐1 Using Combinatorial Chemistry Prismawan, Deka van der Vlag, Ramon Guo, Hao Dekker, Frank J. Hirsch, Anna K. H. Helv Chim Acta Communications Human 15‐lipoxygenase‐1 (15‐LOX‐1) belongs to the class of lipoxygenases, which catalyze oxygenation of polyunsaturated fatty acids, such as arachidonic and linoleic acid. Recent studies have shown that 15‐LOX‐1 plays an important role in physiological processes linked to several diseases such as airway inflammation disease, coronary artery disease, and several types of cancer such as rectal, colon, breast and prostate cancer. In this study, we aimed to extend the structural diversity of 15‐LOX‐1 inhibitors, starting from the recently identified indolyl core. In order to find new scaffolds, we employed a combinatorial approach using various aromatic aldehydes and an aliphatic hydrazide tail. This scaffold‐hopping study resulted in the identification of the 3‐pyridylring as a suitable replacement of the indolyl core with an inhibitory activity in the micromolar range (IC (50)=16±6 μm) and a rapid and efficient structure–activity relationship investigation. John Wiley and Sons Inc. 2019-05-02 2019-05 /pmc/articles/PMC6563716/ /pubmed/31231138 http://dx.doi.org/10.1002/hlca.201900040 Text en © 2019 The Authors. Helvetica Chimica Acta Published by Wiley‐VHCA AG, Zurich, Switzerland This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Communications Prismawan, Deka van der Vlag, Ramon Guo, Hao Dekker, Frank J. Hirsch, Anna K. H. Replacement of an Indole Scaffold Targeting Human 15‐Lipoxygenase‐1 Using Combinatorial Chemistry |
title | Replacement of an Indole Scaffold Targeting Human 15‐Lipoxygenase‐1 Using Combinatorial Chemistry |
title_full | Replacement of an Indole Scaffold Targeting Human 15‐Lipoxygenase‐1 Using Combinatorial Chemistry |
title_fullStr | Replacement of an Indole Scaffold Targeting Human 15‐Lipoxygenase‐1 Using Combinatorial Chemistry |
title_full_unstemmed | Replacement of an Indole Scaffold Targeting Human 15‐Lipoxygenase‐1 Using Combinatorial Chemistry |
title_short | Replacement of an Indole Scaffold Targeting Human 15‐Lipoxygenase‐1 Using Combinatorial Chemistry |
title_sort | replacement of an indole scaffold targeting human 15‐lipoxygenase‐1 using combinatorial chemistry |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563716/ https://www.ncbi.nlm.nih.gov/pubmed/31231138 http://dx.doi.org/10.1002/hlca.201900040 |
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