Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents
Metastatic cancer is considered a fatal progression of cancer worldwide. It has been shown that a key player in this scenario is the CXC chemokine receptor 2 (CXCR2). To identify novel CXCR2 antagonists, a pharmacophore model was built with the HipHop program by screening a database containing compo...
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| Format: | Article |
| Language: | English |
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The Royal Society
2018-01-01
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| Series: | Royal Society Open Science |
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| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.180176 |
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doaj-76f67b191ec847ff9670207842bc59782020-11-25T03:44:24ZengThe Royal SocietyRoyal Society Open Science2054-57032018-01-015710.1098/rsos.180176180176Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agentsJinxin CheZhilong WangHaichao ShengFeng HuangXiaowu DongYouhong HuXin XieYongzhou HuMetastatic cancer is considered a fatal progression of cancer worldwide. It has been shown that a key player in this scenario is the CXC chemokine receptor 2 (CXCR2). To identify novel CXCR2 antagonists, a pharmacophore model was built with the HipHop program by screening a database containing compounds which were designed based on the known structure–activity relationship (SAR) of the diarylurea series CXCR2 antagonists. Compound 1a bearing the novel skeleton was selected from database screening and subjected to the in vitro biological test which showed a moderate CXCR2 antagonist potential. With further modification and exploration of SAR, compound 1e demonstrated improved CXCR2 antagonist activity with an IC50 value of 14.8 µM. Furthermore, wound healing assay using the NCI-H1299 cell line indicated that 1e showed an excellent anti-cancer metastatic effect (72% inhibition in cell migration at 50 µg ml−1).https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.180176pharmacophore modelcxcr2antagonistsanti-cancer metastasis |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Jinxin Che Zhilong Wang Haichao Sheng Feng Huang Xiaowu Dong Youhong Hu Xin Xie Yongzhou Hu |
| spellingShingle |
Jinxin Che Zhilong Wang Haichao Sheng Feng Huang Xiaowu Dong Youhong Hu Xin Xie Yongzhou Hu Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents Royal Society Open Science pharmacophore model cxcr2 antagonists anti-cancer metastasis |
| author_facet |
Jinxin Che Zhilong Wang Haichao Sheng Feng Huang Xiaowu Dong Youhong Hu Xin Xie Yongzhou Hu |
| author_sort |
Jinxin Che |
| title |
Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents |
| title_short |
Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents |
| title_full |
Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents |
| title_fullStr |
Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents |
| title_full_unstemmed |
Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as anti-cancer metastatic agents |
| title_sort |
ligand-based pharmacophore model for the discovery of novel cxcr2 antagonists as anti-cancer metastatic agents |
| publisher |
The Royal Society |
| series |
Royal Society Open Science |
| issn |
2054-5703 |
| publishDate |
2018-01-01 |
| description |
Metastatic cancer is considered a fatal progression of cancer worldwide. It has been shown that a key player in this scenario is the CXC chemokine receptor 2 (CXCR2). To identify novel CXCR2 antagonists, a pharmacophore model was built with the HipHop program by screening a database containing compounds which were designed based on the known structure–activity relationship (SAR) of the diarylurea series CXCR2 antagonists. Compound 1a bearing the novel skeleton was selected from database screening and subjected to the in vitro biological test which showed a moderate CXCR2 antagonist potential. With further modification and exploration of SAR, compound 1e demonstrated improved CXCR2 antagonist activity with an IC50 value of 14.8 µM. Furthermore, wound healing assay using the NCI-H1299 cell line indicated that 1e showed an excellent anti-cancer metastatic effect (72% inhibition in cell migration at 50 µg ml−1). |
| topic |
pharmacophore model cxcr2 antagonists anti-cancer metastasis |
| url |
https://royalsocietypublishing.org/doi/pdf/10.1098/rsos.180176 |
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