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Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3-seco-Tirucallane Triterpenoids Meliadubins A and B from Melia dubia Cav. Barks with ChemGPS-NP and In Silico Prediction

[Image: see text] Two new rearranged 2,3-seco-tirucallane triterpenoids, meliadubins A (1) and B (2), along with four known compounds, 3–6, were isolated from the barks of Melia dubia Cav. Compound 2 exhibited a significant inflammatory inhibition effect toward superoxide anion generation in human n...

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Autores principales: Trung, Hieu Tran, Purnomo, Kartiko Arif, Yu, Szu-Yin, Yang, Zih-Jie, Hu, Hao-Chun, Hwang, Tsong-Long, Tuan, Nguyen Ngoc, Tu, Le Ngoc, Duc, Dau Xuan, Quang, Le Dang, Backlund, Anders, Thang, Tran Dinh, Chang, Fang-Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568771/
https://www.ncbi.nlm.nih.gov/pubmed/37841162
http://dx.doi.org/10.1021/acsomega.3c04657
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author Trung, Hieu Tran
Purnomo, Kartiko Arif
Yu, Szu-Yin
Yang, Zih-Jie
Hu, Hao-Chun
Hwang, Tsong-Long
Tuan, Nguyen Ngoc
Tu, Le Ngoc
Duc, Dau Xuan
Quang, Le Dang
Backlund, Anders
Thang, Tran Dinh
Chang, Fang-Rong
author_facet Trung, Hieu Tran
Purnomo, Kartiko Arif
Yu, Szu-Yin
Yang, Zih-Jie
Hu, Hao-Chun
Hwang, Tsong-Long
Tuan, Nguyen Ngoc
Tu, Le Ngoc
Duc, Dau Xuan
Quang, Le Dang
Backlund, Anders
Thang, Tran Dinh
Chang, Fang-Rong
author_sort Trung, Hieu Tran
collection PubMed
description [Image: see text] Two new rearranged 2,3-seco-tirucallane triterpenoids, meliadubins A (1) and B (2), along with four known compounds, 3–6, were isolated from the barks of Melia dubia Cav. Compound 2 exhibited a significant inflammatory inhibition effect toward superoxide anion generation in human neutrophils (EC(50) at 5.54 ± 0.36 μM). It bound to active sites of a human inducible nitric oxide synthase (3E7G) through interactions with the residues of GLU377 and PRO350, which may benefit in reducing the neutrophilic inflammation effect. The ChemGPS-NP interpretation combined with bioactivity assay and in silico prediction results suggested 2 to be an agent for targeting iNOS with different mechanisms as compared to a selected set of current approved drugs. Moreover, compounds 1 and 2 showed remarkable inhibition against the rice pathogenic fungus Magnaporthe oryzae in a dose-dependent manner with IC(50) values of 137.20 ± 9.55 and 182.50 ± 18.27 μM, respectively. Both 1 and 2 displayed interactions with the residue of TYR223, a key active site of trihydroxynaphthalene reductase (1YBV). The interpretation of 1 and 2 in the ChemGPS-NP physical-chemical property space indicated that both compounds are quite different compared to all members of a selected set of reference compounds. In light of demonstrated biological activity and in silico prediction experiments, both compounds possibly exhibited activity against phytopathogenic fungi via a novel mode of action.
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spelling pubmed-105687712023-10-13 Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3-seco-Tirucallane Triterpenoids Meliadubins A and B from Melia dubia Cav. Barks with ChemGPS-NP and In Silico Prediction Trung, Hieu Tran Purnomo, Kartiko Arif Yu, Szu-Yin Yang, Zih-Jie Hu, Hao-Chun Hwang, Tsong-Long Tuan, Nguyen Ngoc Tu, Le Ngoc Duc, Dau Xuan Quang, Le Dang Backlund, Anders Thang, Tran Dinh Chang, Fang-Rong ACS Omega [Image: see text] Two new rearranged 2,3-seco-tirucallane triterpenoids, meliadubins A (1) and B (2), along with four known compounds, 3–6, were isolated from the barks of Melia dubia Cav. Compound 2 exhibited a significant inflammatory inhibition effect toward superoxide anion generation in human neutrophils (EC(50) at 5.54 ± 0.36 μM). It bound to active sites of a human inducible nitric oxide synthase (3E7G) through interactions with the residues of GLU377 and PRO350, which may benefit in reducing the neutrophilic inflammation effect. The ChemGPS-NP interpretation combined with bioactivity assay and in silico prediction results suggested 2 to be an agent for targeting iNOS with different mechanisms as compared to a selected set of current approved drugs. Moreover, compounds 1 and 2 showed remarkable inhibition against the rice pathogenic fungus Magnaporthe oryzae in a dose-dependent manner with IC(50) values of 137.20 ± 9.55 and 182.50 ± 18.27 μM, respectively. Both 1 and 2 displayed interactions with the residue of TYR223, a key active site of trihydroxynaphthalene reductase (1YBV). The interpretation of 1 and 2 in the ChemGPS-NP physical-chemical property space indicated that both compounds are quite different compared to all members of a selected set of reference compounds. In light of demonstrated biological activity and in silico prediction experiments, both compounds possibly exhibited activity against phytopathogenic fungi via a novel mode of action. American Chemical Society 2023-09-27 /pmc/articles/PMC10568771/ /pubmed/37841162 http://dx.doi.org/10.1021/acsomega.3c04657 Text en © 2023 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by-nc-nd/4.0/Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Trung, Hieu Tran
Purnomo, Kartiko Arif
Yu, Szu-Yin
Yang, Zih-Jie
Hu, Hao-Chun
Hwang, Tsong-Long
Tuan, Nguyen Ngoc
Tu, Le Ngoc
Duc, Dau Xuan
Quang, Le Dang
Backlund, Anders
Thang, Tran Dinh
Chang, Fang-Rong
Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3-seco-Tirucallane Triterpenoids Meliadubins A and B from Melia dubia Cav. Barks with ChemGPS-NP and In Silico Prediction
title Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3-seco-Tirucallane Triterpenoids Meliadubins A and B from Melia dubia Cav. Barks with ChemGPS-NP and In Silico Prediction
title_full Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3-seco-Tirucallane Triterpenoids Meliadubins A and B from Melia dubia Cav. Barks with ChemGPS-NP and In Silico Prediction
title_fullStr Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3-seco-Tirucallane Triterpenoids Meliadubins A and B from Melia dubia Cav. Barks with ChemGPS-NP and In Silico Prediction
title_full_unstemmed Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3-seco-Tirucallane Triterpenoids Meliadubins A and B from Melia dubia Cav. Barks with ChemGPS-NP and In Silico Prediction
title_short Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3-seco-Tirucallane Triterpenoids Meliadubins A and B from Melia dubia Cav. Barks with ChemGPS-NP and In Silico Prediction
title_sort anti-inflammatory and antiphytopathogenic fungal activity of 2,3-seco-tirucallane triterpenoids meliadubins a and b from melia dubia cav. barks with chemgps-np and in silico prediction
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568771/
https://www.ncbi.nlm.nih.gov/pubmed/37841162
http://dx.doi.org/10.1021/acsomega.3c04657
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