Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation
A series of novel N-alkyl-N-hydroxyl carboximates derived from β-elemene were fortuitously discovered. Most of them showed more potent anti-proliferative activities than their lead compound β-elemene (1). Notably, compound 11i exhibited significant inhibitory effects on the proliferation of three lu...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2117314 |
| _version_ | 1828229991129677824 |
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| author | Yuan Gao Nian-Dong Mao Hao Che Li Xu Renren Bai Li-Wei Wang Xiang-Yang Ye Tian Xie |
| author_facet | Yuan Gao Nian-Dong Mao Hao Che Li Xu Renren Bai Li-Wei Wang Xiang-Yang Ye Tian Xie |
| author_sort | Yuan Gao |
| collection | DOAJ |
| description | A series of novel N-alkyl-N-hydroxyl carboximates derived from β-elemene were fortuitously discovered. Most of them showed more potent anti-proliferative activities than their lead compound β-elemene (1). Notably, compound 11i exhibited significant inhibitory effects on the proliferation of three lung cell lines (H1975, A549 and H460) and several other tumour cell lines (H1299, U87MG, MV4-11, and SU-DHL-2). Preliminary mechanistic studies revealed that compound 11i could significantly induce cell apoptosis. Further in vivo study in the H460 xenograft mouse model validated the anti-tumour activities of 11i with a greater tumour growth inhibition (TGI, 68.3%) than β-elemene and SAHA (50.1% and 55.9% respectively) at 60 mg/kg ip dosing, without obvious body weight loss and toxicity. Thus, such N-alkyl-N-hydroxyl carboximate class of compounds exemplified as 11i demonstrated potent anticancer activities both in vitro and in vivo, and should warrant further investigation for potential anticancer therapy. |
| first_indexed | 2024-04-12T18:41:33Z |
| format | Article |
| id | doaj.art-707aa9ee081e4afea07d1d5c814c1b9d |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-12T18:41:33Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-707aa9ee081e4afea07d1d5c814c1b9d2022-12-22T03:20:45ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013712403241610.1080/14756366.2022.2117314Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluationYuan Gao0Nian-Dong Mao1Hao Che2Li Xu3Renren Bai4Li-Wei Wang5Xiang-Yang Ye6Tian Xie7School of Pharmacy, Hangzhou Normal University, Hangzhou, ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou, ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou, ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou, ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou, ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou, ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou, ChinaSchool of Pharmacy, Hangzhou Normal University, Hangzhou, ChinaA series of novel N-alkyl-N-hydroxyl carboximates derived from β-elemene were fortuitously discovered. Most of them showed more potent anti-proliferative activities than their lead compound β-elemene (1). Notably, compound 11i exhibited significant inhibitory effects on the proliferation of three lung cell lines (H1975, A549 and H460) and several other tumour cell lines (H1299, U87MG, MV4-11, and SU-DHL-2). Preliminary mechanistic studies revealed that compound 11i could significantly induce cell apoptosis. Further in vivo study in the H460 xenograft mouse model validated the anti-tumour activities of 11i with a greater tumour growth inhibition (TGI, 68.3%) than β-elemene and SAHA (50.1% and 55.9% respectively) at 60 mg/kg ip dosing, without obvious body weight loss and toxicity. Thus, such N-alkyl-N-hydroxyl carboximate class of compounds exemplified as 11i demonstrated potent anticancer activities both in vitro and in vivo, and should warrant further investigation for potential anticancer therapy.https://www.tandfonline.com/doi/10.1080/14756366.2022.2117314β-elemenehydroxyl carboximate derivativesanti-tumour drugslung cancer |
| spellingShingle | Yuan Gao Nian-Dong Mao Hao Che Li Xu Renren Bai Li-Wei Wang Xiang-Yang Ye Tian Xie Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation Journal of Enzyme Inhibition and Medicinal Chemistry β-elemene hydroxyl carboximate derivatives anti-tumour drugs lung cancer |
| title | Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation |
| title_full | Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation |
| title_fullStr | Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation |
| title_full_unstemmed | Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation |
| title_short | Novel hydroxyl carboximates derived from β-elemene: design, synthesis and anti-tumour activities evaluation |
| title_sort | novel hydroxyl carboximates derived from β elemene design synthesis and anti tumour activities evaluation |
| topic | β-elemene hydroxyl carboximate derivatives anti-tumour drugs lung cancer |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2117314 |
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