Design, synthesis and biological evaluation of novel nitric oxidedonating protoberberine derivatives as antitumor agents
A novel class of NO-donating protoberberine derivatives were synthesized and initially evaluated for their anti-hepatocellular carcinoma activities. Most of the compounds exhibited more potent activity against HepG2 cells than parent compounds berberine and palmatine. In particular, compound 15a exe...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Published: |
Elsevier
2017
|
| Subjects: | |
| Online Access: | https://eprints.nottingham.ac.uk/42904/ |
| _version_ | 1848796597990719488 |
|---|---|
| author | Chen, Jichao Wang, Tianyu Xu, Shengtao Lin, Aijun Yao, Hequan Xie, Weijia Zhu, Zheying Xu, Jinyi |
| author_facet | Chen, Jichao Wang, Tianyu Xu, Shengtao Lin, Aijun Yao, Hequan Xie, Weijia Zhu, Zheying Xu, Jinyi |
| author_sort | Chen, Jichao |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | A novel class of NO-donating protoberberine derivatives were synthesized and initially evaluated for their anti-hepatocellular carcinoma activities. Most of the compounds exhibited more potent activity against HepG2 cells than parent compounds berberine and palmatine. In particular, compound 15a exerted the strongest activity with an IC50 value of 1.36 μM. Moreover, most compounds released moderate levels of NO in vitro, and the antitumor activity of 15a in HepG2 cells was remarkably diminished by an NO scavenger. Interestingly, compound 15a displayed a broad-spectrum antitumor efficacy and possessed good selectivity between tumor cells (HepG2, SMMC-7721, HCT-116, HL-60) and normal liver LO-2 cells. The mechanism studies revealed that 15a blocked the G2 phase of the cell cycle and induced apoptosis of HepG2 cells by mitochondrial depolarization. Furthermore, 15a inhibited tumor growth in H22 liver cancer xenograft mouse model by 62.5% (w/w), which was significantly superior to parent compound palmatine (41.6%, w/w). Overall, the current study may provide a new approach for the discovery of novel antitumor agents. |
| first_indexed | 2025-11-14T19:50:31Z |
| format | Article |
| id | nottingham-42904 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:50:31Z |
| publishDate | 2017 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-429042020-05-04T18:46:56Z https://eprints.nottingham.ac.uk/42904/ Design, synthesis and biological evaluation of novel nitric oxidedonating protoberberine derivatives as antitumor agents Chen, Jichao Wang, Tianyu Xu, Shengtao Lin, Aijun Yao, Hequan Xie, Weijia Zhu, Zheying Xu, Jinyi A novel class of NO-donating protoberberine derivatives were synthesized and initially evaluated for their anti-hepatocellular carcinoma activities. Most of the compounds exhibited more potent activity against HepG2 cells than parent compounds berberine and palmatine. In particular, compound 15a exerted the strongest activity with an IC50 value of 1.36 μM. Moreover, most compounds released moderate levels of NO in vitro, and the antitumor activity of 15a in HepG2 cells was remarkably diminished by an NO scavenger. Interestingly, compound 15a displayed a broad-spectrum antitumor efficacy and possessed good selectivity between tumor cells (HepG2, SMMC-7721, HCT-116, HL-60) and normal liver LO-2 cells. The mechanism studies revealed that 15a blocked the G2 phase of the cell cycle and induced apoptosis of HepG2 cells by mitochondrial depolarization. Furthermore, 15a inhibited tumor growth in H22 liver cancer xenograft mouse model by 62.5% (w/w), which was significantly superior to parent compound palmatine (41.6%, w/w). Overall, the current study may provide a new approach for the discovery of novel antitumor agents. Elsevier 2017-05-26 Article PeerReviewed Chen, Jichao, Wang, Tianyu, Xu, Shengtao, Lin, Aijun, Yao, Hequan, Xie, Weijia, Zhu, Zheying and Xu, Jinyi (2017) Design, synthesis and biological evaluation of novel nitric oxidedonating protoberberine derivatives as antitumor agents. European Journal of Medicinal Chemistry, 132 . pp. 173-183. ISSN 0223-5234 Berberine; Palmatine; Nitric oxide (NO) donor; Hybrid compound; Antitumor activity http://www.sciencedirect.com/science/article/pii/S0223523417301848 doi:10.1016/j.ejmech.2017.03.027 doi:10.1016/j.ejmech.2017.03.027 |
| spellingShingle | Berberine; Palmatine; Nitric oxide (NO) donor; Hybrid compound; Antitumor activity Chen, Jichao Wang, Tianyu Xu, Shengtao Lin, Aijun Yao, Hequan Xie, Weijia Zhu, Zheying Xu, Jinyi Design, synthesis and biological evaluation of novel nitric oxidedonating protoberberine derivatives as antitumor agents |
| title | Design, synthesis and biological evaluation of novel nitric oxidedonating protoberberine derivatives as antitumor agents |
| title_full | Design, synthesis and biological evaluation of novel nitric oxidedonating protoberberine derivatives as antitumor agents |
| title_fullStr | Design, synthesis and biological evaluation of novel nitric oxidedonating protoberberine derivatives as antitumor agents |
| title_full_unstemmed | Design, synthesis and biological evaluation of novel nitric oxidedonating protoberberine derivatives as antitumor agents |
| title_short | Design, synthesis and biological evaluation of novel nitric oxidedonating protoberberine derivatives as antitumor agents |
| title_sort | design, synthesis and biological evaluation of novel nitric oxidedonating protoberberine derivatives as antitumor agents |
| topic | Berberine; Palmatine; Nitric oxide (NO) donor; Hybrid compound; Antitumor activity |
| url | https://eprints.nottingham.ac.uk/42904/ https://eprints.nottingham.ac.uk/42904/ https://eprints.nottingham.ac.uk/42904/ |