Design, synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of SHP2 phosphatase
A series of novel triazoloquinolinone and imidazoquinazolinone derivatives were designed and synthesised, and their biological activities against SHP2 protein and melanoma A357 cell line were evaluated in vitro. The results show that some target compounds have moderate to excellent inhibitory activi...
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| 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 |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2078968 |
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| author | Wenjun Ye Ye Liu Qian Ren Tianhui Liao Yumei Chen Dongmei Chen Sisi Wang Lihong Yao Yihe Jia Chunshen Zhao Zhixu Zhou |
| author_facet | Wenjun Ye Ye Liu Qian Ren Tianhui Liao Yumei Chen Dongmei Chen Sisi Wang Lihong Yao Yihe Jia Chunshen Zhao Zhixu Zhou |
| author_sort | Wenjun Ye |
| collection | DOAJ |
| description | A series of novel triazoloquinolinone and imidazoquinazolinone derivatives were designed and synthesised, and their biological activities against SHP2 protein and melanoma A357 cell line were evaluated in vitro. The results show that some target compounds have moderate to excellent inhibitory activity on SHP2 protein and melanoma A357 cell line. Structure-activity relationships (SARs) showed that both imidazoquinazolinone and triazoloquinazolinone derivatives have good SHP2 protein kinase and melanoma cell line A357 inhibitory activity. The results of molecular docking also showed that the cores of imidazoquinazolinone and triazoloquinazolinone have a certain affinity for SHP2 protein at the same time. Compared with SHP244, the target compounds have quite good liver microsomal stability and has more drug potential. The most promising compound B1 has a strong inhibitory effect on the melanoma cell line A357 at 100 µM (76.15% inhibition). |
| format | Article |
| id | doaj-art-6550e0a7a59648c1afab4fea3f48fc2e |
| institution | Kabale University |
| 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-6550e0a7a59648c1afab4fea3f48fc2e2025-08-20T03:31:27ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013711495151310.1080/14756366.2022.2078968Design, synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of SHP2 phosphataseWenjun Ye0Ye Liu1Qian Ren2Tianhui Liao3Yumei Chen4Dongmei Chen5Sisi Wang6Lihong Yao7Yihe Jia8Chunshen Zhao9Zhixu Zhou10School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, ChinaSchool of Pharmaceutical Sciences, Guizhou University, Guiyang, China;School of Pharmaceutical Sciences, Guizhou University, Guiyang, China;A series of novel triazoloquinolinone and imidazoquinazolinone derivatives were designed and synthesised, and their biological activities against SHP2 protein and melanoma A357 cell line were evaluated in vitro. The results show that some target compounds have moderate to excellent inhibitory activity on SHP2 protein and melanoma A357 cell line. Structure-activity relationships (SARs) showed that both imidazoquinazolinone and triazoloquinazolinone derivatives have good SHP2 protein kinase and melanoma cell line A357 inhibitory activity. The results of molecular docking also showed that the cores of imidazoquinazolinone and triazoloquinazolinone have a certain affinity for SHP2 protein at the same time. Compared with SHP244, the target compounds have quite good liver microsomal stability and has more drug potential. The most promising compound B1 has a strong inhibitory effect on the melanoma cell line A357 at 100 µM (76.15% inhibition).https://www.tandfonline.com/doi/10.1080/14756366.2022.2078968SHP2allosteric inhibitorssynthesisantitumor activity |
| spellingShingle | Wenjun Ye Ye Liu Qian Ren Tianhui Liao Yumei Chen Dongmei Chen Sisi Wang Lihong Yao Yihe Jia Chunshen Zhao Zhixu Zhou Design, synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of SHP2 phosphatase Journal of Enzyme Inhibition and Medicinal Chemistry SHP2 allosteric inhibitors synthesis antitumor activity |
| title | Design, synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of SHP2 phosphatase |
| title_full | Design, synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of SHP2 phosphatase |
| title_fullStr | Design, synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of SHP2 phosphatase |
| title_full_unstemmed | Design, synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of SHP2 phosphatase |
| title_short | Design, synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of SHP2 phosphatase |
| title_sort | design synthesis and biological evaluation of novel triazoloquinazolinone and imidazoquinazolinone derivatives as allosteric inhibitors of shp2 phosphatase |
| topic | SHP2 allosteric inhibitors synthesis antitumor activity |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2078968 |
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