Synthesis and anticancer properties of celastrol derivatives involved in the inhibition of VEGF
In this study, fourteen celastrol derivatives (1–14) were synthesised by esterification of celastrol at the 29th position. The in vitro anticancer activity of them was determined by the MTT assay. All the synthetic compounds showed significant antiproliferative activity against six cancer cells, wit...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2238137 |
| _version_ | 1827123347529400320 |
|---|---|
| author | Mingxia Song Jiantao Wen Yi Hua Yangnv Zhu Qishan Xia Qiaoyue Guo Yiqin Luo Xianqing Deng Yushan Huang |
| author_facet | Mingxia Song Jiantao Wen Yi Hua Yangnv Zhu Qishan Xia Qiaoyue Guo Yiqin Luo Xianqing Deng Yushan Huang |
| author_sort | Mingxia Song |
| collection | DOAJ |
| description | In this study, fourteen celastrol derivatives (1–14) were synthesised by esterification of celastrol at the 29th position. The in vitro anticancer activity of them was determined by the MTT assay. All the synthetic compounds showed significant antiproliferative activity against six cancer cells, with IC50 of the submicron molar level. The most promising compound (2) blocked the cell cycle in the G2 phase and inhibited the expression of VEGF and MMP-9 in gastric cancer cell line MGC-803. In flow cytometry analysis, compound 2 induced cancer cell apoptosis in a dose-dependent manner. In the mouse tumour xenograft model, compound 2 showed significant anti-tumour activity in vivo at the dosage of 2.5 mg/kg and 1 mg/kg, with a higher inhibition rate than 5-FU (10 mg/kg). What’s more, the anticancer mechanism involved in the inhibition of VEGF and the toxicity evaluation of compound 2 were also investigated. |
| first_indexed | 2024-03-09T02:02:51Z |
| format | Article |
| id | doaj.art-73c155fcb7664122aa9fa1c4c1594b74 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2025-03-20T14:23:29Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-73c155fcb7664122aa9fa1c4c1594b742024-09-09T17:23:19ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2238137Synthesis and anticancer properties of celastrol derivatives involved in the inhibition of VEGFMingxia Song0Jiantao Wen1Yi Hua2Yangnv Zhu3Qishan Xia4Qiaoyue Guo5Yiqin Luo6Xianqing Deng7Yushan Huang8Affiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Jinggangshan University, Ji’an, Jiangxi, ChinaAffiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Jinggangshan University, Ji’an, Jiangxi, ChinaAffiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Jinggangshan University, Ji’an, Jiangxi, ChinaAffiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Jinggangshan University, Ji’an, Jiangxi, ChinaAffiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Jinggangshan University, Ji’an, Jiangxi, ChinaAffiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Jinggangshan University, Ji’an, Jiangxi, ChinaAffiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Jinggangshan University, Ji’an, Jiangxi, ChinaAffiliated Hospital of Jinggangshan University, Center for Clinical Medicine Research of Jinggangshan University, Jinggangshan University, Ji’an, Jiangxi, ChinaCenter for Evidence-Based Medical and Clinical Research, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaIn this study, fourteen celastrol derivatives (1–14) were synthesised by esterification of celastrol at the 29th position. The in vitro anticancer activity of them was determined by the MTT assay. All the synthetic compounds showed significant antiproliferative activity against six cancer cells, with IC50 of the submicron molar level. The most promising compound (2) blocked the cell cycle in the G2 phase and inhibited the expression of VEGF and MMP-9 in gastric cancer cell line MGC-803. In flow cytometry analysis, compound 2 induced cancer cell apoptosis in a dose-dependent manner. In the mouse tumour xenograft model, compound 2 showed significant anti-tumour activity in vivo at the dosage of 2.5 mg/kg and 1 mg/kg, with a higher inhibition rate than 5-FU (10 mg/kg). What’s more, the anticancer mechanism involved in the inhibition of VEGF and the toxicity evaluation of compound 2 were also investigated.https://www.tandfonline.com/doi/10.1080/14756366.2023.2238137CelastrolanticancerantitumormodificationVEGF |
| spellingShingle | Mingxia Song Jiantao Wen Yi Hua Yangnv Zhu Qishan Xia Qiaoyue Guo Yiqin Luo Xianqing Deng Yushan Huang Synthesis and anticancer properties of celastrol derivatives involved in the inhibition of VEGF Journal of Enzyme Inhibition and Medicinal Chemistry Celastrol anticancer antitumor modification VEGF |
| title | Synthesis and anticancer properties of celastrol derivatives involved in the inhibition of VEGF |
| title_full | Synthesis and anticancer properties of celastrol derivatives involved in the inhibition of VEGF |
| title_fullStr | Synthesis and anticancer properties of celastrol derivatives involved in the inhibition of VEGF |
| title_full_unstemmed | Synthesis and anticancer properties of celastrol derivatives involved in the inhibition of VEGF |
| title_short | Synthesis and anticancer properties of celastrol derivatives involved in the inhibition of VEGF |
| title_sort | synthesis and anticancer properties of celastrol derivatives involved in the inhibition of vegf |
| topic | Celastrol anticancer antitumor modification VEGF |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2238137 |
| work_keys_str_mv | AT mingxiasong synthesisandanticancerpropertiesofcelastrolderivativesinvolvedintheinhibitionofvegf AT jiantaowen synthesisandanticancerpropertiesofcelastrolderivativesinvolvedintheinhibitionofvegf AT yihua synthesisandanticancerpropertiesofcelastrolderivativesinvolvedintheinhibitionofvegf AT yangnvzhu synthesisandanticancerpropertiesofcelastrolderivativesinvolvedintheinhibitionofvegf AT qishanxia synthesisandanticancerpropertiesofcelastrolderivativesinvolvedintheinhibitionofvegf AT qiaoyueguo synthesisandanticancerpropertiesofcelastrolderivativesinvolvedintheinhibitionofvegf AT yiqinluo synthesisandanticancerpropertiesofcelastrolderivativesinvolvedintheinhibitionofvegf AT xianqingdeng synthesisandanticancerpropertiesofcelastrolderivativesinvolvedintheinhibitionofvegf AT yushanhuang synthesisandanticancerpropertiesofcelastrolderivativesinvolvedintheinhibitionofvegf |