Synthesis and Biological Evaluation of Sclareolide-Indole Conjugates and Their Derivatives
Sclareolide is a sesquiterpene lactone isolated from various plant sources in tons every year and is commercially used as a flavor ingredient in the cosmetic and food industries. Antitumor and antiviral activities of sclareolide have been previously reported. However, biological studies of sclareoli...
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/4/1737 |
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| author | Ying Cheng Xilin Lyu Chen Liu Xiancheng Wang Jing Cheng Daizhou Zhang Xiangjing Meng Yujun Zhao |
| author_facet | Ying Cheng Xilin Lyu Chen Liu Xiancheng Wang Jing Cheng Daizhou Zhang Xiangjing Meng Yujun Zhao |
| author_sort | Ying Cheng |
| collection | DOAJ |
| description | Sclareolide is a sesquiterpene lactone isolated from various plant sources in tons every year and is commercially used as a flavor ingredient in the cosmetic and food industries. Antitumor and antiviral activities of sclareolide have been previously reported. However, biological studies of sclareolide synthetic analogous are few. In view of these, we developed a robust synthetic method that allows the assembly of 36 novel sclareolide-indole conjugates and their derivatives. The synthetic method was based on TiCl<sub>4</sub>-promoted nucleophilic substitution of sclareolide-derived hemiacetal <b>4</b>, while electron-rich aryles including indoles, polyphenol ethers, and pyrazolo [1,5-a]pyridine were good substrates. The stereochemistry of the final products was confirmed by single-crystal X-ray diffraction analysis, while the antiproliferative activities of selected final products were tested in K562 and MV4-11 cancer cell lines. Cytometric flow analysis shows that lead compounds <b>8k</b>- and <b>10</b>-induced robust apoptosis in MV4-11 cancer cells, while they exhibited weak impact on cell cycle progression. Taken together, our study suggests that sclareolide could be a good template and substrate for the synthesis of novel antiproliferative compounds. |
| first_indexed | 2024-03-11T08:22:06Z |
| format | Article |
| id | doaj.art-5e046996a660439fa9b6c44b2748ce50 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T08:22:06Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-5e046996a660439fa9b6c44b2748ce502023-11-16T22:22:34ZengMDPI AGMolecules1420-30492023-02-01284173710.3390/molecules28041737Synthesis and Biological Evaluation of Sclareolide-Indole Conjugates and Their DerivativesYing Cheng0Xilin Lyu1Chen Liu2Xiancheng Wang3Jing Cheng4Daizhou Zhang5Xiangjing Meng6Yujun Zhao7School of Chinese Materia Medica, Nanjing University of Chinese Medicine; Nanjing 210023, ChinaState Key Laboratory of Drug Research and Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Rd., Shanghai 201203, ChinaSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine; Nanjing 210023, ChinaState Key Laboratory of Drug Research and Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Rd., Shanghai 201203, ChinaState Key Laboratory of Drug Research and Small-Molecule Drug Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Rd., Shanghai 201203, ChinaShandong Provincial Key Laboratory of Biopharmaceuticals, Shandong Academy of Pharmaceutical Sciences, Jinan 250101, ChinaShandong Provincial Key Laboratory of Biopharmaceuticals, Shandong Academy of Pharmaceutical Sciences, Jinan 250101, ChinaSchool of Chinese Materia Medica, Nanjing University of Chinese Medicine; Nanjing 210023, ChinaSclareolide is a sesquiterpene lactone isolated from various plant sources in tons every year and is commercially used as a flavor ingredient in the cosmetic and food industries. Antitumor and antiviral activities of sclareolide have been previously reported. However, biological studies of sclareolide synthetic analogous are few. In view of these, we developed a robust synthetic method that allows the assembly of 36 novel sclareolide-indole conjugates and their derivatives. The synthetic method was based on TiCl<sub>4</sub>-promoted nucleophilic substitution of sclareolide-derived hemiacetal <b>4</b>, while electron-rich aryles including indoles, polyphenol ethers, and pyrazolo [1,5-a]pyridine were good substrates. The stereochemistry of the final products was confirmed by single-crystal X-ray diffraction analysis, while the antiproliferative activities of selected final products were tested in K562 and MV4-11 cancer cell lines. Cytometric flow analysis shows that lead compounds <b>8k</b>- and <b>10</b>-induced robust apoptosis in MV4-11 cancer cells, while they exhibited weak impact on cell cycle progression. Taken together, our study suggests that sclareolide could be a good template and substrate for the synthesis of novel antiproliferative compounds.https://www.mdpi.com/1420-3049/28/4/1737sclareolideindolepolyphenolacetalantitumor activity |
| spellingShingle | Ying Cheng Xilin Lyu Chen Liu Xiancheng Wang Jing Cheng Daizhou Zhang Xiangjing Meng Yujun Zhao Synthesis and Biological Evaluation of Sclareolide-Indole Conjugates and Their Derivatives Molecules sclareolide indole polyphenol acetal antitumor activity |
| title | Synthesis and Biological Evaluation of Sclareolide-Indole Conjugates and Their Derivatives |
| title_full | Synthesis and Biological Evaluation of Sclareolide-Indole Conjugates and Their Derivatives |
| title_fullStr | Synthesis and Biological Evaluation of Sclareolide-Indole Conjugates and Their Derivatives |
| title_full_unstemmed | Synthesis and Biological Evaluation of Sclareolide-Indole Conjugates and Their Derivatives |
| title_short | Synthesis and Biological Evaluation of Sclareolide-Indole Conjugates and Their Derivatives |
| title_sort | synthesis and biological evaluation of sclareolide indole conjugates and their derivatives |
| topic | sclareolide indole polyphenol acetal antitumor activity |
| url | https://www.mdpi.com/1420-3049/28/4/1737 |
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