Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity
Harringtonolide (HO), a natural product isolated from <i>Cephalotaxus harringtonia</i>, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone,...
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MDPI AG
2021-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/5/1380 |
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| author | Xiutao Wu Lijie Gong Chen Chen Ye Tao Wuxi Zhou Lingyi Kong Jianguang Luo |
| author_facet | Xiutao Wu Lijie Gong Chen Chen Ye Tao Wuxi Zhou Lingyi Kong Jianguang Luo |
| author_sort | Xiutao Wu |
| collection | DOAJ |
| description | Harringtonolide (HO), a natural product isolated from <i>Cephalotaxus harringtonia</i>, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO (<b>1</b>) were carried out to provide 17 derivatives (<b>2</b>–<b>13, 11a</b>–<b>11f</b>). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound <b>6</b> exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO. |
| first_indexed | 2024-03-09T05:31:49Z |
| format | Article |
| id | doaj.art-f3797f56611c4a49a72d1cef71e141f8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T05:31:49Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj.art-f3797f56611c4a49a72d1cef71e141f82023-12-03T12:32:06ZengMDPI AGMolecules1420-30492021-03-01265138010.3390/molecules26051380Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative ActivityXiutao Wu0Lijie Gong1Chen Chen2Ye Tao3Wuxi Zhou4Lingyi Kong5Jianguang Luo6State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, ChinaState Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Bioactive Natural Product Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, ChinaHarringtonolide (HO), a natural product isolated from <i>Cephalotaxus harringtonia</i>, exhibits potent antiproliferative activity. However, little information has been reported on the systematic structure−activity relationship (SAR) of HO derivatives. Modifications on tropone, lactone, and allyl positions of HO (<b>1</b>) were carried out to provide 17 derivatives (<b>2</b>–<b>13, 11a</b>–<b>11f</b>). The in vitro antiproliferative activity against four cancer cell lines (HCT-116, A375, A549, and Huh-7) and one normal cell line (L-02) was tested. Amongst these novel derivatives, compound <b>6</b> exhibited comparable cell growth inhibitory activity to HO and displayed better selectivity index (SI = 56.5) between Huh-7 and L-02 cells. The SAR results revealed that the tropone and lactone moieties are essential for the cytotoxic activities, which provided useful suggestions for further structural optimization of HO.https://www.mdpi.com/1420-3049/26/5/1380harringtonolidetroponoidsstructure-activity relationship (SAR)antiproliferative activity |
| spellingShingle | Xiutao Wu Lijie Gong Chen Chen Ye Tao Wuxi Zhou Lingyi Kong Jianguang Luo Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity Molecules harringtonolide troponoids structure-activity relationship (SAR) antiproliferative activity |
| title | Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity |
| title_full | Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity |
| title_fullStr | Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity |
| title_full_unstemmed | Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity |
| title_short | Semi-Synthesis of Harringtonolide Derivatives and Their Antiproliferative Activity |
| title_sort | semi synthesis of harringtonolide derivatives and their antiproliferative activity |
| topic | harringtonolide troponoids structure-activity relationship (SAR) antiproliferative activity |
| url | https://www.mdpi.com/1420-3049/26/5/1380 |
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