Polyketides with Cardioprotective Bioactivities from Sponge-Associated Fungus <i>Aspergillus giganteus</i> MA46-5

One pair of novel enantiomers, gigantdioxin A (+)-<b>1</b> and B (−)-<b>1</b>, with a skeleton of benzo[<i>d</i>][1,3]dioxin; a new acetophenone gigantone A (<b>3</b>); a known 3-chlorogentisyl alcohol (<b>2</b>), which is the bioprecursor...

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Main Authors: Ying-Tong Lin, Xiao-Wei Yao, Zheng-Wu Luo, Wei-Xin Jiang, Yin-Fei Wu, Ze-Jun Li, Xue-Wei Duan, Meng-Dan Zhang, Yuan-Yuan Cheng, Cui-Xian Zhang
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Language:English
Published: MDPI AG 2025-04-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/7/1632
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author Ying-Tong Lin
Xiao-Wei Yao
Zheng-Wu Luo
Wei-Xin Jiang
Yin-Fei Wu
Ze-Jun Li
Xue-Wei Duan
Meng-Dan Zhang
Yuan-Yuan Cheng
Cui-Xian Zhang
author_facet Ying-Tong Lin
Xiao-Wei Yao
Zheng-Wu Luo
Wei-Xin Jiang
Yin-Fei Wu
Ze-Jun Li
Xue-Wei Duan
Meng-Dan Zhang
Yuan-Yuan Cheng
Cui-Xian Zhang
author_sort Ying-Tong Lin
collection DOAJ
description One pair of novel enantiomers, gigantdioxin A (+)-<b>1</b> and B (−)-<b>1</b>, with a skeleton of benzo[<i>d</i>][1,3]dioxin; a new acetophenone gigantone A (<b>3</b>); a known 3-chlorogentisyl alcohol (<b>2</b>), which is the bioprecursor of <b>1</b>; acetophenone (<b>4</b>); and chromone derivative (<b>5</b>) were obtained from the sponge-associated fungus <i>Aspergillus giganteus</i> MA46-5. Their structures were established by extensive and in-depth spectral analysis, such as UV, 1D and 2D NMR, and HRESIMS. The absolute configurations of (±)-<b>1</b> were deduced by ORD, chiral separation, and experimental and computational ECD. Meanwhile, we proposed a possible biosynthetic pathway of (±)-<b>1</b>. Fortunately, the pathway was proved by biomimetic synthesis through <b>2</b>, as a bioprecursor, reacted with <i>n</i>-butyraldehyde. Myocardial protection assays showed that <b>3</b> and <b>4</b> possessed stronger protective effects than a positive control against myocardial cell H9c2 ischemia–reperfusion injury in low concentrations, and the effect of (−)-<b>1</b> was almost equal to that of the positive control. Further, we explored the possible mechanism of myocardial protection through network pharmacology. Adenosine A2a receptor (ADORA2A) and serum albumin (ALB) represent potential targets for myocardial protection associated with (−)-<b>1</b> and <b>4</b>, respectively. Based on the network pharmacology, we docked the predicted proteins with bioactive compounds using Autodock Vina.
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spelling doaj-art-caab59646548499cbb7592f48122a3fd2025-08-20T02:17:01ZengMDPI AGMolecules1420-30492025-04-01307163210.3390/molecules30071632Polyketides with Cardioprotective Bioactivities from Sponge-Associated Fungus <i>Aspergillus giganteus</i> MA46-5Ying-Tong Lin0Xiao-Wei Yao1Zheng-Wu Luo2Wei-Xin Jiang3Yin-Fei Wu4Ze-Jun Li5Xue-Wei Duan6Meng-Dan Zhang7Yuan-Yuan Cheng8Cui-Xian Zhang9School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, ChinaOne pair of novel enantiomers, gigantdioxin A (+)-<b>1</b> and B (−)-<b>1</b>, with a skeleton of benzo[<i>d</i>][1,3]dioxin; a new acetophenone gigantone A (<b>3</b>); a known 3-chlorogentisyl alcohol (<b>2</b>), which is the bioprecursor of <b>1</b>; acetophenone (<b>4</b>); and chromone derivative (<b>5</b>) were obtained from the sponge-associated fungus <i>Aspergillus giganteus</i> MA46-5. Their structures were established by extensive and in-depth spectral analysis, such as UV, 1D and 2D NMR, and HRESIMS. The absolute configurations of (±)-<b>1</b> were deduced by ORD, chiral separation, and experimental and computational ECD. Meanwhile, we proposed a possible biosynthetic pathway of (±)-<b>1</b>. Fortunately, the pathway was proved by biomimetic synthesis through <b>2</b>, as a bioprecursor, reacted with <i>n</i>-butyraldehyde. Myocardial protection assays showed that <b>3</b> and <b>4</b> possessed stronger protective effects than a positive control against myocardial cell H9c2 ischemia–reperfusion injury in low concentrations, and the effect of (−)-<b>1</b> was almost equal to that of the positive control. Further, we explored the possible mechanism of myocardial protection through network pharmacology. Adenosine A2a receptor (ADORA2A) and serum albumin (ALB) represent potential targets for myocardial protection associated with (−)-<b>1</b> and <b>4</b>, respectively. Based on the network pharmacology, we docked the predicted proteins with bioactive compounds using Autodock Vina.https://www.mdpi.com/1420-3049/30/7/1632sponge-associated fungus<i>Aspergillus giganteus</i> MA46-5polyketidesmyocardial protection
spellingShingle Ying-Tong Lin
Xiao-Wei Yao
Zheng-Wu Luo
Wei-Xin Jiang
Yin-Fei Wu
Ze-Jun Li
Xue-Wei Duan
Meng-Dan Zhang
Yuan-Yuan Cheng
Cui-Xian Zhang
Polyketides with Cardioprotective Bioactivities from Sponge-Associated Fungus <i>Aspergillus giganteus</i> MA46-5
Molecules
sponge-associated fungus
<i>Aspergillus giganteus</i> MA46-5
polyketides
myocardial protection
title Polyketides with Cardioprotective Bioactivities from Sponge-Associated Fungus <i>Aspergillus giganteus</i> MA46-5
title_full Polyketides with Cardioprotective Bioactivities from Sponge-Associated Fungus <i>Aspergillus giganteus</i> MA46-5
title_fullStr Polyketides with Cardioprotective Bioactivities from Sponge-Associated Fungus <i>Aspergillus giganteus</i> MA46-5
title_full_unstemmed Polyketides with Cardioprotective Bioactivities from Sponge-Associated Fungus <i>Aspergillus giganteus</i> MA46-5
title_short Polyketides with Cardioprotective Bioactivities from Sponge-Associated Fungus <i>Aspergillus giganteus</i> MA46-5
title_sort polyketides with cardioprotective bioactivities from sponge associated fungus i aspergillus giganteus i ma46 5
topic sponge-associated fungus
<i>Aspergillus giganteus</i> MA46-5
polyketides
myocardial protection
url https://www.mdpi.com/1420-3049/30/7/1632
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