Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors
AbstractInhibition of PI3K pathway has become a desirable strategy for cancer treatment. In this work, a series of 2, 6, 8-substituted Imidazo[1,2-a]pyridine derivatives were designed and screened for their activities against PI3Kα and a panel of PI3Kα-addicted cancer cells. Among them, compound 35...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2022.2155638 |
| _version_ | 1797400944794664960 |
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| author | Rui Chen Zhongyuan Wang Lijie Sima Hu Cheng Bilan Luo Jianta Wang Bing Guo Shunyi Mao Zhixu Zhou Jingang Peng Lei Tang Xinfu Liu Weike Liao |
| author_facet | Rui Chen Zhongyuan Wang Lijie Sima Hu Cheng Bilan Luo Jianta Wang Bing Guo Shunyi Mao Zhixu Zhou Jingang Peng Lei Tang Xinfu Liu Weike Liao |
| author_sort | Rui Chen |
| collection | DOAJ |
| description | AbstractInhibition of PI3K pathway has become a desirable strategy for cancer treatment. In this work, a series of 2, 6, 8-substituted Imidazo[1,2-a]pyridine derivatives were designed and screened for their activities against PI3Kα and a panel of PI3Kα-addicted cancer cells. Among them, compound 35 was identified as a PI3Kα inhibitor with nanomolar potency as well as acceptable antiproliferative activity. Flow cytometry analysis confirmed 35 induced cell cycle arrest and apoptosis in T47D cells. In addition, it also showed desirable in vitro ADME properties. The design, synthesis, and SAR exploration of 35 are described within. |
| first_indexed | 2024-03-09T02:02:50Z |
| format | Article |
| id | doaj.art-6e1797e3188e4735aad8d0d57f0377db |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-09T02:02:50Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-6e1797e3188e4735aad8d0d57f0377db2023-12-08T03:24:20ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2022.2155638Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitorsRui Chen0Zhongyuan Wang1Lijie Sima2Hu Cheng3Bilan Luo4Jianta Wang5Bing Guo6Shunyi Mao7Zhixu Zhou8Jingang Peng9Lei Tang10Xinfu Liu11Weike Liao12Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, ChinaDepartment of Pharmacy, Guizhou Provincial People’s Hospital, Guiyang, ChinaDepartment of Hematology and Oncology, The Affiliated Shaoyang Hospital, Hengyang Medical School, University of South China (Shaoyang Central Hospital), ChinaGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, ChinaGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, ChinaGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, ChinaGuizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, ChinaSchool of Pharmaceutical Sciences, Guizhou University, Guiyang, ChinaSchool of Pharmaceutical Sciences, Guizhou University, Guiyang, ChinaGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, ChinaGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, ChinaDepartment of Hematology and Oncology, The Affiliated Shaoyang Hospital, Hengyang Medical School, University of South China (Shaoyang Central Hospital), ChinaGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, Guiyang, ChinaAbstractInhibition of PI3K pathway has become a desirable strategy for cancer treatment. In this work, a series of 2, 6, 8-substituted Imidazo[1,2-a]pyridine derivatives were designed and screened for their activities against PI3Kα and a panel of PI3Kα-addicted cancer cells. Among them, compound 35 was identified as a PI3Kα inhibitor with nanomolar potency as well as acceptable antiproliferative activity. Flow cytometry analysis confirmed 35 induced cell cycle arrest and apoptosis in T47D cells. In addition, it also showed desirable in vitro ADME properties. The design, synthesis, and SAR exploration of 35 are described within.https://www.tandfonline.com/doi/10.1080/14756366.2022.2155638PI3KαsynthesisImidazo[12-a]pyridine derivativesantitumor activity |
| spellingShingle | Rui Chen Zhongyuan Wang Lijie Sima Hu Cheng Bilan Luo Jianta Wang Bing Guo Shunyi Mao Zhixu Zhou Jingang Peng Lei Tang Xinfu Liu Weike Liao Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry PI3Kα synthesis Imidazo[12-a]pyridine derivatives antitumor activity |
| title | Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors |
| title_full | Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors |
| title_fullStr | Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors |
| title_full_unstemmed | Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors |
| title_short | Design, synthesis and evaluation of 2, 6, 8-substituted Imidazopyridine derivatives as potent PI3Kα inhibitors |
| title_sort | design synthesis and evaluation of 2 6 8 substituted imidazopyridine derivatives as potent pi3kα inhibitors |
| topic | PI3Kα synthesis Imidazo[12-a]pyridine derivatives antitumor activity |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2155638 |
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