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Effects of Daidzin and analogue of Ganoderma sinense on bacterially-expressed human hexokinase isoform 2 for anti-dengue drug design

Dengue disease, which is caused by dengue virus (DENV) has been a major worldwide concern, with increased number of cases each year. Currently, there are no specific medications to treat the disease. Hence, there is a dire need to develop novel drugs for disease treatment. Glycolysis is a metabolic...

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Main Authors: Asman, Nur Atikah, Tanbin, Suriyea, Ahmad Fuad, Fazia Adyani
Format: Article
Language:English
Published: IIUM Press 2020
Subjects:
Q Science (General)
QD Chemistry
RM Therapeutics. Pharmacology
Online Access:http://irep.iium.edu.my/87086/1/87086_effects%20off%20daidzin%20and%20analogue%20off%20ganoderma%20sinensetin_ft.pdf
http://irep.iium.edu.my/87086/
https://journals.iium.edu.my/bnrej/index.php/bnrej/article/view/48
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spelling my.iium.irep.870862022-03-17T08:29:59Z http://irep.iium.edu.my/87086/ Effects of Daidzin and analogue of Ganoderma sinense on bacterially-expressed human hexokinase isoform 2 for anti-dengue drug design Asman, Nur Atikah Tanbin, Suriyea Ahmad Fuad, Fazia Adyani Q Science (General) QD Chemistry RM Therapeutics. Pharmacology Dengue disease, which is caused by dengue virus (DENV) has been a major worldwide concern, with increased number of cases each year. Currently, there are no specific medications to treat the disease. Hence, there is a dire need to develop novel drugs for disease treatment. Glycolysis is a metabolic pathway that serves as the main source of energy for DENV replication and targeting the pathway is one of the ideal approach to discover new anti-DENV drugs. This paper focuses on the inhibition of the human hexokinase isoform 2 (HK2) enzyme, which is one of the important enzymes in glycolysis, in the quest to disrupt DENV replication. In order to search for potential inhibitors, two methods were conducted, which are ligand-based screening and structure-based screening approaches. The docking of Daidzin, which was derived from Kudzu, a Japanese plant, has shown the nearest binding affinity score (-7.94 kcal/mol) to Glucose‘s (GLC), which is -8.15 kcal/mol. Meanwhile, from the ligand-based screening, Ethyl (2R)-2-[[3-[2-[(4-methylbenzoyl)amino]ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]sulfanyl]butanoate, a compound which is the analogue of Ganoderma sinense with a binding score of -8.43 kcal/mol was chosen for the subsequent inhibition studies. These compounds were further analysed in an inhibition assay to determine the effects of of the potential naturally-derived inhibitors on the activity of HK2. The outcome from the inhibition study shows that both compounds exhibited substantial inhibition on HK2 enzyme, where Daidzin, at 0.5 mM, resulted in HK2 remaining activity of 88.98%, while Ethyl (2R)-2-[[3-[2-[(4-methylbenzoyl)amino]ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]sulfanyl]butanoate (Ethyl (2R)) resulted in 69.58% of HK2 remaining activity, also at 0.5 mM concentration. In conclusion, this study has served as a platform for the development of anti-dengue drugs based on naturally-derived compounds, which is anticipated to be a safer option for dengue treatment IIUM Press 2020-12-28 Article PeerReviewed application/pdf en http://irep.iium.edu.my/87086/1/87086_effects%20off%20daidzin%20and%20analogue%20off%20ganoderma%20sinensetin_ft.pdf Asman, Nur Atikah and Tanbin, Suriyea and Ahmad Fuad, Fazia Adyani (2020) Effects of Daidzin and analogue of Ganoderma sinense on bacterially-expressed human hexokinase isoform 2 for anti-dengue drug design. Biological And Natural Resources Engineering Journal, 3 (2). pp. 27-34. E-ISSN 2637-0719 https://journals.iium.edu.my/bnrej/index.php/bnrej/article/view/48
institution Universiti Islam Antarabangsa Malaysia
building IIUM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider International Islamic University Malaysia
content_source IIUM Repository (IREP)
url_provider http://irep.iium.edu.my/
language English
topic Q Science (General)
QD Chemistry
RM Therapeutics. Pharmacology
spellingShingle Q Science (General)
QD Chemistry
RM Therapeutics. Pharmacology
Asman, Nur Atikah
Tanbin, Suriyea
Ahmad Fuad, Fazia Adyani
Effects of Daidzin and analogue of Ganoderma sinense on bacterially-expressed human hexokinase isoform 2 for anti-dengue drug design
description Dengue disease, which is caused by dengue virus (DENV) has been a major worldwide concern, with increased number of cases each year. Currently, there are no specific medications to treat the disease. Hence, there is a dire need to develop novel drugs for disease treatment. Glycolysis is a metabolic pathway that serves as the main source of energy for DENV replication and targeting the pathway is one of the ideal approach to discover new anti-DENV drugs. This paper focuses on the inhibition of the human hexokinase isoform 2 (HK2) enzyme, which is one of the important enzymes in glycolysis, in the quest to disrupt DENV replication. In order to search for potential inhibitors, two methods were conducted, which are ligand-based screening and structure-based screening approaches. The docking of Daidzin, which was derived from Kudzu, a Japanese plant, has shown the nearest binding affinity score (-7.94 kcal/mol) to Glucose‘s (GLC), which is -8.15 kcal/mol. Meanwhile, from the ligand-based screening, Ethyl (2R)-2-[[3-[2-[(4-methylbenzoyl)amino]ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]sulfanyl]butanoate, a compound which is the analogue of Ganoderma sinense with a binding score of -8.43 kcal/mol was chosen for the subsequent inhibition studies. These compounds were further analysed in an inhibition assay to determine the effects of of the potential naturally-derived inhibitors on the activity of HK2. The outcome from the inhibition study shows that both compounds exhibited substantial inhibition on HK2 enzyme, where Daidzin, at 0.5 mM, resulted in HK2 remaining activity of 88.98%, while Ethyl (2R)-2-[[3-[2-[(4-methylbenzoyl)amino]ethyl]-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]sulfanyl]butanoate (Ethyl (2R)) resulted in 69.58% of HK2 remaining activity, also at 0.5 mM concentration. In conclusion, this study has served as a platform for the development of anti-dengue drugs based on naturally-derived compounds, which is anticipated to be a safer option for dengue treatment
format Article
author Asman, Nur Atikah
Tanbin, Suriyea
Ahmad Fuad, Fazia Adyani
author_facet Asman, Nur Atikah
Tanbin, Suriyea
Ahmad Fuad, Fazia Adyani
author_sort Asman, Nur Atikah
title Effects of Daidzin and analogue of Ganoderma sinense on bacterially-expressed human hexokinase isoform 2 for anti-dengue drug design
title_short Effects of Daidzin and analogue of Ganoderma sinense on bacterially-expressed human hexokinase isoform 2 for anti-dengue drug design
title_full Effects of Daidzin and analogue of Ganoderma sinense on bacterially-expressed human hexokinase isoform 2 for anti-dengue drug design
title_fullStr Effects of Daidzin and analogue of Ganoderma sinense on bacterially-expressed human hexokinase isoform 2 for anti-dengue drug design
title_full_unstemmed Effects of Daidzin and analogue of Ganoderma sinense on bacterially-expressed human hexokinase isoform 2 for anti-dengue drug design
title_sort effects of daidzin and analogue of ganoderma sinense on bacterially-expressed human hexokinase isoform 2 for anti-dengue drug design
publisher IIUM Press
publishDate 2020
url http://irep.iium.edu.my/87086/1/87086_effects%20off%20daidzin%20and%20analogue%20off%20ganoderma%20sinensetin_ft.pdf
http://irep.iium.edu.my/87086/
https://journals.iium.edu.my/bnrej/index.php/bnrej/article/view/48
_version_ 1728051150693859328
score 13.211869

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