Light-Mediated Transformation of Renieramycins and Semisynthesis of 4′-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells
The semisynthesis of renieramycin-type derivatives was achieved under mild and facile conditions by attaching a 1,3-dioxole-bridged phenolic moiety onto ring A of the renieramycin structure and adding a 4′-pyridinecarbonyl ester substituent at its C-5 or C-22 position. These were accomplished throug...
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2023-07-01
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| author | Suwimon Sinsook Koonchira Buaban Iksen Iksen Korrakod Petsri Bhurichaya Innets Chaisak Chansriniyom Khanit Suwanborirux Masashi Yokoya Naoki Saito Varisa Pongrakhananon Pithi Chanvorachote Supakarn Chamni |
| author_facet | Suwimon Sinsook Koonchira Buaban Iksen Iksen Korrakod Petsri Bhurichaya Innets Chaisak Chansriniyom Khanit Suwanborirux Masashi Yokoya Naoki Saito Varisa Pongrakhananon Pithi Chanvorachote Supakarn Chamni |
| author_sort | Suwimon Sinsook |
| collection | DOAJ |
| description | The semisynthesis of renieramycin-type derivatives was achieved under mild and facile conditions by attaching a 1,3-dioxole-bridged phenolic moiety onto ring A of the renieramycin structure and adding a 4′-pyridinecarbonyl ester substituent at its C-5 or C-22 position. These were accomplished through a light-induced intramolecular photoredox reaction using blue light (4 W) and Steglich esterification, respectively. Renieramycin M (<b>4</b>), a bis-tetrahydroisoquinolinequinone compound isolated from the Thai blue sponge (<i>Xestospongia</i> sp.), served as the starting material. The cytotoxicity of the 10 natural and semisynthesized renieramycins against non-small-cell lung cancer (NSCLC) cell lines was evaluated. The 5-<i>O</i>-(4′-pyridinecarbonyl) renieramycin T (<b>11</b>) compound exhibited high cytotoxicity with half-maximal inhibitory concentration (IC<sub>50</sub>) values of 35.27 ± 1.09 and 34.77 ± 2.19 nM against H290 and H460 cells, respectively. Notably, the potency of compound <b>11</b> was 2-fold more than that of renieramycin T (<b>7</b>) and equal to those of <b>4</b> and doxorubicin. Interestingly, the renieramycin-type derivatives with a hydroxyl group at C-5 and C-22 exhibited weak cytotoxicity. In silico molecular docking and dynamics studies confirmed that the mitogen-activated proteins, kinase 1 and 3 (MAPK1 and MAPK3), are suitable targets for <b>11</b>. Thus, the structure–cytotoxicity study of renieramycins was extended to facilitate the development of potential anticancer agents for NSCLC cells. |
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| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-11T00:52:32Z |
| publishDate | 2023-07-01 |
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| series | Marine Drugs |
| spelling | doaj.art-19302a8038654f77ab95cdce144e7eaf2023-11-18T20:14:17ZengMDPI AGMarine Drugs1660-33972023-07-0121740010.3390/md21070400Light-Mediated Transformation of Renieramycins and Semisynthesis of 4′-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer CellsSuwimon Sinsook0Koonchira Buaban1Iksen Iksen2Korrakod Petsri3Bhurichaya Innets4Chaisak Chansriniyom5Khanit Suwanborirux6Masashi Yokoya7Naoki Saito8Varisa Pongrakhananon9Pithi Chanvorachote10Supakarn Chamni11Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandGraduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Tokyo 204-8588, JapanGraduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Tokyo 204-8588, JapanDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, ThailandThe semisynthesis of renieramycin-type derivatives was achieved under mild and facile conditions by attaching a 1,3-dioxole-bridged phenolic moiety onto ring A of the renieramycin structure and adding a 4′-pyridinecarbonyl ester substituent at its C-5 or C-22 position. These were accomplished through a light-induced intramolecular photoredox reaction using blue light (4 W) and Steglich esterification, respectively. Renieramycin M (<b>4</b>), a bis-tetrahydroisoquinolinequinone compound isolated from the Thai blue sponge (<i>Xestospongia</i> sp.), served as the starting material. The cytotoxicity of the 10 natural and semisynthesized renieramycins against non-small-cell lung cancer (NSCLC) cell lines was evaluated. The 5-<i>O</i>-(4′-pyridinecarbonyl) renieramycin T (<b>11</b>) compound exhibited high cytotoxicity with half-maximal inhibitory concentration (IC<sub>50</sub>) values of 35.27 ± 1.09 and 34.77 ± 2.19 nM against H290 and H460 cells, respectively. Notably, the potency of compound <b>11</b> was 2-fold more than that of renieramycin T (<b>7</b>) and equal to those of <b>4</b> and doxorubicin. Interestingly, the renieramycin-type derivatives with a hydroxyl group at C-5 and C-22 exhibited weak cytotoxicity. In silico molecular docking and dynamics studies confirmed that the mitogen-activated proteins, kinase 1 and 3 (MAPK1 and MAPK3), are suitable targets for <b>11</b>. Thus, the structure–cytotoxicity study of renieramycins was extended to facilitate the development of potential anticancer agents for NSCLC cells.https://www.mdpi.com/1660-3397/21/7/400<i>Xestospongia</i> sp.cytotoxicityrenieramycinssemisynthesislight-induced intramolecular photoredox reactionnon-small-cell lung cancer |
| spellingShingle | Suwimon Sinsook Koonchira Buaban Iksen Iksen Korrakod Petsri Bhurichaya Innets Chaisak Chansriniyom Khanit Suwanborirux Masashi Yokoya Naoki Saito Varisa Pongrakhananon Pithi Chanvorachote Supakarn Chamni Light-Mediated Transformation of Renieramycins and Semisynthesis of 4′-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells Marine Drugs <i>Xestospongia</i> sp. cytotoxicity renieramycins semisynthesis light-induced intramolecular photoredox reaction non-small-cell lung cancer |
| title | Light-Mediated Transformation of Renieramycins and Semisynthesis of 4′-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells |
| title_full | Light-Mediated Transformation of Renieramycins and Semisynthesis of 4′-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells |
| title_fullStr | Light-Mediated Transformation of Renieramycins and Semisynthesis of 4′-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells |
| title_full_unstemmed | Light-Mediated Transformation of Renieramycins and Semisynthesis of 4′-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells |
| title_short | Light-Mediated Transformation of Renieramycins and Semisynthesis of 4′-Pyridinecarbonyl-Substituted Renieramycin-Type Derivatives as Potential Cytotoxic Agents against Non-Small-Cell Lung Cancer Cells |
| title_sort | light mediated transformation of renieramycins and semisynthesis of 4 pyridinecarbonyl substituted renieramycin type derivatives as potential cytotoxic agents against non small cell lung cancer cells |
| topic | <i>Xestospongia</i> sp. cytotoxicity renieramycins semisynthesis light-induced intramolecular photoredox reaction non-small-cell lung cancer |
| url | https://www.mdpi.com/1660-3397/21/7/400 |
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