Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic Agents
2,5-Bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-teraahydro-6<i>H</i>-pyran[<i>a</i>]isoindol-2-yl]-pentanoic acid (FGFC1) is a marine pyran-isoindolone derivative isolated from a rare marine microorganism <i>Stachybotrys longispora</i&...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/19/4/218 |
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| author | Yinan Wang Hui Chen Ruilong Sheng Zhe Fu Junting Fan Wenhui Wu Qidong Tu Ruihua Guo |
| author_facet | Yinan Wang Hui Chen Ruilong Sheng Zhe Fu Junting Fan Wenhui Wu Qidong Tu Ruihua Guo |
| author_sort | Yinan Wang |
| collection | DOAJ |
| description | 2,5-Bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-teraahydro-6<i>H</i>-pyran[<i>a</i>]isoindol-2-yl]-pentanoic acid (FGFC1) is a marine pyran-isoindolone derivative isolated from a rare marine microorganism <i>Stachybotrys longispora</i> FG216, which showed moderate antithrombotic(fibrinolytic) activity. To further enhance its antithrombotic effect, a series of new FGFC1 derivatives (<b>F1</b>–<b>F7</b>) were synthesized via chemical modification at C-2 and C-2′ phenol groups moieties and C-1″ carboxyl group. Their fibrinolytic activities in vitro were evaluated. Among the derivatives, <b>F1</b>–<b>F4</b> and <b>F6</b> showed significant fibrinolytic activities with EC<sub>50</sub> of 59.7, 87.1, 66.6, 82.8, and 42.3 μM, respectively, via enhancement of urokinase activity. Notably, derivative <b>F6</b> presented the most remarkable fibrinolytic activity (2.72-fold than that of FGFC1). Furthermore, the cytotoxicity of derivative <b>F6</b> was tested as well as expression of Fas/Apo-1 and IL-1 on HeLa cells. The results showed that, compared to FGFC1, derivative <b>F6</b> possessed moderate cytotoxicity and apoptotic effect on HeLa cells (statistical significance <i>p</i> > 0.1), making <b>F6</b> a potential antithrombotic agent towards clinical application. |
| first_indexed | 2024-03-10T12:17:12Z |
| format | Article |
| id | doaj.art-48209d54405f41dab58f8065af94043c |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T12:17:12Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-48209d54405f41dab58f8065af94043c2023-11-21T15:45:40ZengMDPI AGMarine Drugs1660-33972021-04-0119421810.3390/md19040218Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic AgentsYinan Wang0Hui Chen1Ruilong Sheng2Zhe Fu3Junting Fan4Wenhui Wu5Qidong Tu6Ruihua Guo7College of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaShanghai Engineering Research Center of Hadal Science and Technology, College of Marine Sciences, Shanghai Ocean University, Shanghai 201306, ChinaCQM-Centro de Química da Madeira, Campus da Penteada, Universidade da Madeira, 9000-390 Funchal, PortugalCollege of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaSchool of Pharmacy, Nanjing Medical University, Nanjing 211166, ChinaCollege of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, ChinaSchool of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, ChinaCollege of Food Science and Technology, Shanghai Ocean University, Shanghai 201306, China2,5-Bis-[8-(4,8-dimethyl-nona-3,7-dienyl)-5,7-dihydroxy-8-methyl-3-keto-1,2,7,8-teraahydro-6<i>H</i>-pyran[<i>a</i>]isoindol-2-yl]-pentanoic acid (FGFC1) is a marine pyran-isoindolone derivative isolated from a rare marine microorganism <i>Stachybotrys longispora</i> FG216, which showed moderate antithrombotic(fibrinolytic) activity. To further enhance its antithrombotic effect, a series of new FGFC1 derivatives (<b>F1</b>–<b>F7</b>) were synthesized via chemical modification at C-2 and C-2′ phenol groups moieties and C-1″ carboxyl group. Their fibrinolytic activities in vitro were evaluated. Among the derivatives, <b>F1</b>–<b>F4</b> and <b>F6</b> showed significant fibrinolytic activities with EC<sub>50</sub> of 59.7, 87.1, 66.6, 82.8, and 42.3 μM, respectively, via enhancement of urokinase activity. Notably, derivative <b>F6</b> presented the most remarkable fibrinolytic activity (2.72-fold than that of FGFC1). Furthermore, the cytotoxicity of derivative <b>F6</b> was tested as well as expression of Fas/Apo-1 and IL-1 on HeLa cells. The results showed that, compared to FGFC1, derivative <b>F6</b> possessed moderate cytotoxicity and apoptotic effect on HeLa cells (statistical significance <i>p</i> > 0.1), making <b>F6</b> a potential antithrombotic agent towards clinical application.https://www.mdpi.com/1660-3397/19/4/218pyran-isoindolone derivativesantithrombotic agentsfibrinolytic activityPro-uPA-catalyzed plasminogenmodification |
| spellingShingle | Yinan Wang Hui Chen Ruilong Sheng Zhe Fu Junting Fan Wenhui Wu Qidong Tu Ruihua Guo Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic Agents Marine Drugs pyran-isoindolone derivatives antithrombotic agents fibrinolytic activity Pro-uPA-catalyzed plasminogen modification |
| title | Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic Agents |
| title_full | Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic Agents |
| title_fullStr | Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic Agents |
| title_full_unstemmed | Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic Agents |
| title_short | Synthesis and Bioactivities of Marine Pyran-Isoindolone Derivatives as Potential Antithrombotic Agents |
| title_sort | synthesis and bioactivities of marine pyran isoindolone derivatives as potential antithrombotic agents |
| topic | pyran-isoindolone derivatives antithrombotic agents fibrinolytic activity Pro-uPA-catalyzed plasminogen modification |
| url | https://www.mdpi.com/1660-3397/19/4/218 |
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