Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents
The methylation of amino acid residues has played an important role in the biological function of bioactive peptides. In this paper, various methyl-modified and stereostructural-modified marine cyclopeptide galaxamide analogs with isoindolinone were synthesized by a photoinduced single electron tran...
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MDPI AG
2022-06-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/20/6/379 |
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| author | Shimei Xiao Zhiqiang Wang Huanli Zhang Lei Zhao Qingran Chang Xiong Zhang Rui Yan Xiaodan Wu Yingxue Jin |
| author_facet | Shimei Xiao Zhiqiang Wang Huanli Zhang Lei Zhao Qingran Chang Xiong Zhang Rui Yan Xiaodan Wu Yingxue Jin |
| author_sort | Shimei Xiao |
| collection | DOAJ |
| description | The methylation of amino acid residues has played an important role in the biological function of bioactive peptides. In this paper, various methyl-modified and stereostructural-modified marine cyclopeptide galaxamide analogs with isoindolinone were synthesized by a photoinduced single electron transfer cyclization reaction. It was found that the single-methyl substitution was beneficial for the bioactivity of cyclic analogs with isoindolinone fragments, and the influence of methylation on bioactivity is uncertain and is sometimes case-specific. The compound with a single methyl group at Gly<sup>5</sup> (compound <b>8</b>) showed the strongest antiproliferative activity against HepG-2 cells. The tumor cell apoptosis, cell cycle, mitochondrial membrane potential, intracellular Ca<sup>2+</sup> concentration and lactate dehydrogenase activity have been studied extensively to evaluate the antitumor potential of compound <b>8</b>. Western blotting tests showed that compound <b>8</b> could decrease the MDM2 level and increase p53 levels efficiently. Careful molecular docking suggested that cyclic peptide 8 could bind firmly with MDM2 oncoprotein, indicating that MDM2 may be a potential drug target of the prepared peptides. |
| first_indexed | 2024-03-09T23:12:25Z |
| format | Article |
| id | doaj.art-19becb6269e74abfa9a8830dba58b3a1 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T23:12:25Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-19becb6269e74abfa9a8830dba58b3a12023-11-23T17:41:12ZengMDPI AGMarine Drugs1660-33972022-06-0120637910.3390/md20060379Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer AgentsShimei Xiao0Zhiqiang Wang1Huanli Zhang2Lei Zhao3Qingran Chang4Xiong Zhang5Rui Yan6Xiaodan Wu7Yingxue Jin8Key Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, ChinaKey Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, ChinaKey Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, ChinaKey Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, ChinaKey Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, ChinaKey Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, ChinaKey Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, ChinaKey Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, ChinaKey Laboratory of Photochemical Biomaterials and Energy Storage Materials, College of Chemistry & Chemical Engineering, Harbin Normal University, Harbin 150025, ChinaThe methylation of amino acid residues has played an important role in the biological function of bioactive peptides. In this paper, various methyl-modified and stereostructural-modified marine cyclopeptide galaxamide analogs with isoindolinone were synthesized by a photoinduced single electron transfer cyclization reaction. It was found that the single-methyl substitution was beneficial for the bioactivity of cyclic analogs with isoindolinone fragments, and the influence of methylation on bioactivity is uncertain and is sometimes case-specific. The compound with a single methyl group at Gly<sup>5</sup> (compound <b>8</b>) showed the strongest antiproliferative activity against HepG-2 cells. The tumor cell apoptosis, cell cycle, mitochondrial membrane potential, intracellular Ca<sup>2+</sup> concentration and lactate dehydrogenase activity have been studied extensively to evaluate the antitumor potential of compound <b>8</b>. Western blotting tests showed that compound <b>8</b> could decrease the MDM2 level and increase p53 levels efficiently. Careful molecular docking suggested that cyclic peptide 8 could bind firmly with MDM2 oncoprotein, indicating that MDM2 may be a potential drug target of the prepared peptides.https://www.mdpi.com/1660-3397/20/6/379cyclic peptidephotoinduced cyclizationgalaxamideantitumorstereochemistry |
| spellingShingle | Shimei Xiao Zhiqiang Wang Huanli Zhang Lei Zhao Qingran Chang Xiong Zhang Rui Yan Xiaodan Wu Yingxue Jin Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents Marine Drugs cyclic peptide photoinduced cyclization galaxamide antitumor stereochemistry |
| title | Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents |
| title_full | Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents |
| title_fullStr | Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents |
| title_full_unstemmed | Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents |
| title_short | Photoinduced Synthesis of Methylated Marine Cyclopeptide Galaxamide Analogs with Isoindolinone as Anticancer Agents |
| title_sort | photoinduced synthesis of methylated marine cyclopeptide galaxamide analogs with isoindolinone as anticancer agents |
| topic | cyclic peptide photoinduced cyclization galaxamide antitumor stereochemistry |
| url | https://www.mdpi.com/1660-3397/20/6/379 |
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