Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer
A series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound C6 exhibited the most robust inhibition of FTO with an IC50 value of 780 nM. It displayed the potent antiproliferative activity a...
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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 |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2098954 |
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| author | Bo Qin Qian Bai Dan Yan Fanxiang Yin Zhu Zhu Chaoyuan Xia Yang Yang Yi Zhao |
| author_facet | Bo Qin Qian Bai Dan Yan Fanxiang Yin Zhu Zhu Chaoyuan Xia Yang Yang Yi Zhao |
| author_sort | Bo Qin |
| collection | DOAJ |
| description | A series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound C6 exhibited the most robust inhibition of FTO with an IC50 value of 780 nM. It displayed the potent antiproliferative activity against KYSE-150, KYSE-270, TE-1, KYSE-510, and EC109 cell lines with IC50 value of 2.17, 1.35, 0.95, 4.15, and 0.83 μM, respectively. In addition, C6 arrested the cell cycle at G2 phase against TE-1 and EC109 cells in a concentration-dependent manner. Analysis of cellular mechanisms demonstrated that C6 concentration-dependently regulated epithelial mesenchymal transition (EMT) pathway and PI3K/AKT pathway against TE-1 and EC109 cells. Molecular docking studies that C6 formed important hydrogen-bond interaction with Lys107, Asn110, Tyr108, and Leu109 of FTO. These findings suggested that C6 as a novel FTO inhibitor and orally antitumor agent deserves further investigation to treat esophageal cancer. |
| format | Article |
| id | doaj-art-e58db9ffe40344579e77658a6f58986e |
| institution | DOAJ |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-e58db9ffe40344579e77658a6f58986e2025-08-20T03:22:26ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013711995200310.1080/14756366.2022.2098954Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancerBo Qin0Qian Bai1Dan Yan2Fanxiang Yin3Zhu Zhu4Chaoyuan Xia5Yang Yang6Yi Zhao7Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR ChinaDepartment of Anesthesiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, PR ChinaTranslational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR ChinaTranslational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR ChinaTranslational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR ChinaTranslational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR ChinaTranslational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR ChinaTranslational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR ChinaA series of 1,2,3-triazole analogues as novel fat mass and obesity-associated protein (FTO) inhibitors were synthesised in this study. Among all 1,2,3-triazoles, compound C6 exhibited the most robust inhibition of FTO with an IC50 value of 780 nM. It displayed the potent antiproliferative activity against KYSE-150, KYSE-270, TE-1, KYSE-510, and EC109 cell lines with IC50 value of 2.17, 1.35, 0.95, 4.15, and 0.83 μM, respectively. In addition, C6 arrested the cell cycle at G2 phase against TE-1 and EC109 cells in a concentration-dependent manner. Analysis of cellular mechanisms demonstrated that C6 concentration-dependently regulated epithelial mesenchymal transition (EMT) pathway and PI3K/AKT pathway against TE-1 and EC109 cells. Molecular docking studies that C6 formed important hydrogen-bond interaction with Lys107, Asn110, Tyr108, and Leu109 of FTO. These findings suggested that C6 as a novel FTO inhibitor and orally antitumor agent deserves further investigation to treat esophageal cancer.https://www.tandfonline.com/doi/10.1080/14756366.2022.2098954FTO1,2,3-triazoleesophageal cancercell cyclemolecular docking |
| spellingShingle | Bo Qin Qian Bai Dan Yan Fanxiang Yin Zhu Zhu Chaoyuan Xia Yang Yang Yi Zhao Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer Journal of Enzyme Inhibition and Medicinal Chemistry FTO 1,2,3-triazole esophageal cancer cell cycle molecular docking |
| title | Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer |
| title_full | Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer |
| title_fullStr | Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer |
| title_full_unstemmed | Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer |
| title_short | Discovery of novel mRNA demethylase FTO inhibitors against esophageal cancer |
| title_sort | discovery of novel mrna demethylase fto inhibitors against esophageal cancer |
| topic | FTO 1,2,3-triazole esophageal cancer cell cycle molecular docking |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2098954 |
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