Discovery of <i>p</i>-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus <i>Aspergillus</i> sp. ITBBc1
Chemical investigation of the fermentation extract of the coral-associated fungus <i>Aspergillus</i> sp. ITBBc1 led to the discovery of five unreported <i>p</i>-terphenyl derivatives, sanshamycins A–E (<b>1</b>–<b>5</b>), together with five previously...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/20/11/679 |
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| author | Zhikai Guo Ailiman Abulaizi Ling Huang Zijun Xiong Shiqing Zhang Tianmi Liu Rong Wang |
| author_facet | Zhikai Guo Ailiman Abulaizi Ling Huang Zijun Xiong Shiqing Zhang Tianmi Liu Rong Wang |
| author_sort | Zhikai Guo |
| collection | DOAJ |
| description | Chemical investigation of the fermentation extract of the coral-associated fungus <i>Aspergillus</i> sp. ITBBc1 led to the discovery of five unreported <i>p</i>-terphenyl derivatives, sanshamycins A–E (<b>1</b>–<b>5</b>), together with five previously described analogues, terphenyllin (<b>6</b>), 3-hydroxyterphenyllin (<b>7</b>), candidusin A (<b>8</b>), 4,5-dimethoxycandidusin A (<b>9</b>), and candidusin C (<b>10</b>). Their structures were elucidated by HRESIMS data and NMR spectroscopic analysis. Compound <b>1</b> represents the first example of <i>p</i>-terphenyls with an aldehyde substitution on the benzene ring. Compounds <b>2</b>–<b>4</b> feature varying methoxyl and isopentenyl substitutions, while compound <b>5</b> features a five-membered lactone linked to a biphenyl. These findings expand the chemical diversity of the family of <i>p</i>-terphenyl natural products. Compounds <b>1</b>–<b>6</b> and <b>9</b> were evaluated for their inhibitory activity against type 4 phosphodiesterase (PDE4), which is a fascinating drug target for treatment of inflammatory, respiratory, and neurological diseases. Compound <b>3</b> was the most potent and exhibited PDE4D inhibitory activity with an IC<sub>50</sub> value of 5.543 µM. |
| first_indexed | 2024-03-09T18:53:28Z |
| format | Article |
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| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T18:53:28Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-14d6000c925842f4ad1ec4b28061c7ee2023-11-24T05:34:19ZengMDPI AGMarine Drugs1660-33972022-10-01201167910.3390/md20110679Discovery of <i>p</i>-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus <i>Aspergillus</i> sp. ITBBc1Zhikai Guo0Ailiman Abulaizi1Ling Huang2Zijun Xiong3Shiqing Zhang4Tianmi Liu5Rong Wang6Hainan Key Laboratory of Tropical Microbe Resources, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences & Key Laboratory for Biology and Genetic Resources of Tropical Crops of Hainan Province, Hainan Institute for Tropical Agricultural Resources, Haikou 571101, ChinaState Key Laboratory of Pharmaceutical Biotechnology, Institute of Functional Biomolecules, School of Life Sciences, Nanjing University, Nanjing 210023, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570208, ChinaHainan Key Laboratory of Tropical Microbe Resources, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences & Key Laboratory for Biology and Genetic Resources of Tropical Crops of Hainan Province, Hainan Institute for Tropical Agricultural Resources, Haikou 571101, ChinaHainan Key Laboratory of Tropical Microbe Resources, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences & Key Laboratory for Biology and Genetic Resources of Tropical Crops of Hainan Province, Hainan Institute for Tropical Agricultural Resources, Haikou 571101, ChinaHainan Testing Center for the Quality and Safety of Aquatic Products, Hainan Aquatic Technology Extension Station, Haikou 570206, ChinaHainan Provincial Key Laboratory of Tropical Maricultural Technologies, Hainan Academy of Ocean and Fisheries Sciences, Haikou 571126, ChinaChemical investigation of the fermentation extract of the coral-associated fungus <i>Aspergillus</i> sp. ITBBc1 led to the discovery of five unreported <i>p</i>-terphenyl derivatives, sanshamycins A–E (<b>1</b>–<b>5</b>), together with five previously described analogues, terphenyllin (<b>6</b>), 3-hydroxyterphenyllin (<b>7</b>), candidusin A (<b>8</b>), 4,5-dimethoxycandidusin A (<b>9</b>), and candidusin C (<b>10</b>). Their structures were elucidated by HRESIMS data and NMR spectroscopic analysis. Compound <b>1</b> represents the first example of <i>p</i>-terphenyls with an aldehyde substitution on the benzene ring. Compounds <b>2</b>–<b>4</b> feature varying methoxyl and isopentenyl substitutions, while compound <b>5</b> features a five-membered lactone linked to a biphenyl. These findings expand the chemical diversity of the family of <i>p</i>-terphenyl natural products. Compounds <b>1</b>–<b>6</b> and <b>9</b> were evaluated for their inhibitory activity against type 4 phosphodiesterase (PDE4), which is a fascinating drug target for treatment of inflammatory, respiratory, and neurological diseases. Compound <b>3</b> was the most potent and exhibited PDE4D inhibitory activity with an IC<sub>50</sub> value of 5.543 µM.https://www.mdpi.com/1660-3397/20/11/679coral-associated fungus<i>Aspergillus</i> sp.natural products<i>p</i>-terphenylsphosphodiesterase PDE4D inhibitor |
| spellingShingle | Zhikai Guo Ailiman Abulaizi Ling Huang Zijun Xiong Shiqing Zhang Tianmi Liu Rong Wang Discovery of <i>p</i>-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus <i>Aspergillus</i> sp. ITBBc1 Marine Drugs coral-associated fungus <i>Aspergillus</i> sp. natural products <i>p</i>-terphenyls phosphodiesterase PDE4D inhibitor |
| title | Discovery of <i>p</i>-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus <i>Aspergillus</i> sp. ITBBc1 |
| title_full | Discovery of <i>p</i>-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus <i>Aspergillus</i> sp. ITBBc1 |
| title_fullStr | Discovery of <i>p</i>-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus <i>Aspergillus</i> sp. ITBBc1 |
| title_full_unstemmed | Discovery of <i>p</i>-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus <i>Aspergillus</i> sp. ITBBc1 |
| title_short | Discovery of <i>p</i>-Terphenyl Metabolites as Potential Phosphodiesterase PDE4D Inhibitors from the Coral-Associated Fungus <i>Aspergillus</i> sp. ITBBc1 |
| title_sort | discovery of i p i terphenyl metabolites as potential phosphodiesterase pde4d inhibitors from the coral associated fungus i aspergillus i sp itbbc1 |
| topic | coral-associated fungus <i>Aspergillus</i> sp. natural products <i>p</i>-terphenyls phosphodiesterase PDE4D inhibitor |
| url | https://www.mdpi.com/1660-3397/20/11/679 |
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