Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1
Coumarins, which have low toxicity, are present in some natural foods, and are used in various herbal remedies, have attracted interest in recent years because of their potential medicinal properties. In this study, we report the isolation of two natural coumarins, namely umbelliferone (1) and 6-for...
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doaj-b83812153d2a4057bf2f1e48b403d91f2020-11-25T00:55:09ZengMDPI AGMolecules1420-30492017-09-012210160410.3390/molecules22101604molecules22101604Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1Md Yousof Ali0Su Hui Seong1Machireddy Rajeshkumar Reddy2Sung Yong Seo3Jae Sue Choi4Hyun Ah Jung5Department of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Chemistry, Pukyong National University, Busan 48513, KoreaDepartment of Chemistry, Pukyong National University, Busan 48513, KoreaDepartment of Food and Life Science, Pukyong National University, Busan 48513, KoreaDepartment of Food Science and Human Nutrition, Chonbuk National University, Jeonju 54896, KoreaCoumarins, which have low toxicity, are present in some natural foods, and are used in various herbal remedies, have attracted interest in recent years because of their potential medicinal properties. In this study, we report the isolation of two natural coumarins, namely umbelliferone (1) and 6-formyl umbelliferone (2), from Angelica decursiva, and the synthesis of 8-formyl umbelliferone (3) from 1. We investigated the anti-Alzheimer disease (anti-AD) potential of these coumarins by assessing their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Among these coumarins, 2 exhibited poor inhibitory activity against AChE and BChE, and modest activity against BACE1. Structure–activity relationship analysis showed that 2 has an aldehyde group at the C-6 position, and exhibited strong anti-AD activity, whereas the presence or absence of an aldehyde group at the C-8 position reduced the anti-AD activity of 3 and 1, respectively. In addition, 2 exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. A kinetic study revealed that 2 and 3 non-competitively inhibited BACE1. To confirm enzyme inhibition, we predicted the 3D structures of AChE and BACE1, and used AutoDock 4.2 to simulate binding of coumarins to these enzymes. The blind docking studies demonstrated that these molecules could interact with both the catalytic active sites and peripheral anionic sites of AChE and BACE1. Together, our results indicate that 2 has an interesting inhibitory activity in vitro, and can be used in further studies to develop therapeutic modalities for the treatment of AD.https://www.mdpi.com/1420-3049/22/10/1604Angelica decursiva6-formyl umbelliferonecoumarinsBACE1cholinesterasesmolecular docking |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Md Yousof Ali Su Hui Seong Machireddy Rajeshkumar Reddy Sung Yong Seo Jae Sue Choi Hyun Ah Jung |
spellingShingle |
Md Yousof Ali Su Hui Seong Machireddy Rajeshkumar Reddy Sung Yong Seo Jae Sue Choi Hyun Ah Jung Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1 Molecules Angelica decursiva 6-formyl umbelliferone coumarins BACE1 cholinesterases molecular docking |
author_facet |
Md Yousof Ali Su Hui Seong Machireddy Rajeshkumar Reddy Sung Yong Seo Jae Sue Choi Hyun Ah Jung |
author_sort |
Md Yousof Ali |
title |
Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1 |
title_short |
Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1 |
title_full |
Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1 |
title_fullStr |
Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1 |
title_full_unstemmed |
Kinetics and Molecular Docking Studies of 6-Formyl Umbelliferone Isolated from Angelica decursiva as an Inhibitor of Cholinesterase and BACE1 |
title_sort |
kinetics and molecular docking studies of 6-formyl umbelliferone isolated from angelica decursiva as an inhibitor of cholinesterase and bace1 |
publisher |
MDPI AG |
series |
Molecules |
issn |
1420-3049 |
publishDate |
2017-09-01 |
description |
Coumarins, which have low toxicity, are present in some natural foods, and are used in various herbal remedies, have attracted interest in recent years because of their potential medicinal properties. In this study, we report the isolation of two natural coumarins, namely umbelliferone (1) and 6-formyl umbelliferone (2), from Angelica decursiva, and the synthesis of 8-formyl umbelliferone (3) from 1. We investigated the anti-Alzheimer disease (anti-AD) potential of these coumarins by assessing their ability to inhibit acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Among these coumarins, 2 exhibited poor inhibitory activity against AChE and BChE, and modest activity against BACE1. Structure–activity relationship analysis showed that 2 has an aldehyde group at the C-6 position, and exhibited strong anti-AD activity, whereas the presence or absence of an aldehyde group at the C-8 position reduced the anti-AD activity of 3 and 1, respectively. In addition, 2 exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. A kinetic study revealed that 2 and 3 non-competitively inhibited BACE1. To confirm enzyme inhibition, we predicted the 3D structures of AChE and BACE1, and used AutoDock 4.2 to simulate binding of coumarins to these enzymes. The blind docking studies demonstrated that these molecules could interact with both the catalytic active sites and peripheral anionic sites of AChE and BACE1. Together, our results indicate that 2 has an interesting inhibitory activity in vitro, and can be used in further studies to develop therapeutic modalities for the treatment of AD. |
topic |
Angelica decursiva 6-formyl umbelliferone coumarins BACE1 cholinesterases molecular docking |
url |
https://www.mdpi.com/1420-3049/22/10/1604 |
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