Discovery of 2-(4-Acrylamidophenyl)-Quinoline-4-Carboxylic Acid Derivatives as Potent SIRT3 Inhibitors
In discovery of novel SIRT3 inhibitors for the treatment of cancer, a series of 2-(4-acrylamidophenyl)-quinoline-4-carboxylic acid derivatives were designed and synthesized. Among the derived compounds, molecule P6 exhibited SIRT3 inhibitory selectivity with IC50 value of 7.2 µM over SIRT1 (32.6 µM)...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.880067/full |
| _version_ | 1819160965010161664 |
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| author | Qian Hui Xueming Li Wenli Fan Congying Gao Lin Zhang Hongyu Qin Liuya Wei Lei Zhang |
| author_facet | Qian Hui Xueming Li Wenli Fan Congying Gao Lin Zhang Hongyu Qin Liuya Wei Lei Zhang |
| author_sort | Qian Hui |
| collection | DOAJ |
| description | In discovery of novel SIRT3 inhibitors for the treatment of cancer, a series of 2-(4-acrylamidophenyl)-quinoline-4-carboxylic acid derivatives were designed and synthesized. Among the derived compounds, molecule P6 exhibited SIRT3 inhibitory selectivity with IC50 value of 7.2 µM over SIRT1 (32.6 µM) and SIRT2 (33.5 µM). molecular docking analysis revealed a specific binding pattern of P6 in the active site of SIRT3 compared with the bindings in the active site of SIRT1 and SIRT2. In the antiproliferative and colony forming assay, molecule P6 showed potent inhibitory activity against a group of MLLr leukemic cell lines. Further analysis revealed that induction of G0/G1 phase cell cycle arrest and cell differentiation, but not apoptosis, makes contributions to the anticancer effects of P6. Collectively, a potent SIRT3 inhibitor (P6) was discovered as a lead compound for the leukemic differentiation therapy. |
| first_indexed | 2024-12-22T17:04:49Z |
| format | Article |
| id | doaj.art-8ae8b28e3bad4922870e7f700d99ee2d |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-22T17:04:49Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-8ae8b28e3bad4922870e7f700d99ee2d2022-12-21T18:19:13ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-03-011010.3389/fchem.2022.880067880067Discovery of 2-(4-Acrylamidophenyl)-Quinoline-4-Carboxylic Acid Derivatives as Potent SIRT3 InhibitorsQian Hui0Xueming Li1Wenli Fan2Congying Gao3Lin Zhang4Hongyu Qin5Liuya Wei6Lei Zhang7Department of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang, ChinaDepartment of Inorganic Chemistry, School of Pharmacy, Weifang Medical University, Weifang, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang, ChinaDepartment of Inorganic Chemistry, School of Pharmacy, Weifang Medical University, Weifang, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang, ChinaDepartment of Inorganic Chemistry, School of Pharmacy, Weifang Medical University, Weifang, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Weifang Medical University, Weifang, ChinaIn discovery of novel SIRT3 inhibitors for the treatment of cancer, a series of 2-(4-acrylamidophenyl)-quinoline-4-carboxylic acid derivatives were designed and synthesized. Among the derived compounds, molecule P6 exhibited SIRT3 inhibitory selectivity with IC50 value of 7.2 µM over SIRT1 (32.6 µM) and SIRT2 (33.5 µM). molecular docking analysis revealed a specific binding pattern of P6 in the active site of SIRT3 compared with the bindings in the active site of SIRT1 and SIRT2. In the antiproliferative and colony forming assay, molecule P6 showed potent inhibitory activity against a group of MLLr leukemic cell lines. Further analysis revealed that induction of G0/G1 phase cell cycle arrest and cell differentiation, but not apoptosis, makes contributions to the anticancer effects of P6. Collectively, a potent SIRT3 inhibitor (P6) was discovered as a lead compound for the leukemic differentiation therapy.https://www.frontiersin.org/articles/10.3389/fchem.2022.880067/fullSIRT3selective inhibitormixed-lineage leukemiascell cycle arrestdifferentiation |
| spellingShingle | Qian Hui Xueming Li Wenli Fan Congying Gao Lin Zhang Hongyu Qin Liuya Wei Lei Zhang Discovery of 2-(4-Acrylamidophenyl)-Quinoline-4-Carboxylic Acid Derivatives as Potent SIRT3 Inhibitors Frontiers in Chemistry SIRT3 selective inhibitor mixed-lineage leukemias cell cycle arrest differentiation |
| title | Discovery of 2-(4-Acrylamidophenyl)-Quinoline-4-Carboxylic Acid Derivatives as Potent SIRT3 Inhibitors |
| title_full | Discovery of 2-(4-Acrylamidophenyl)-Quinoline-4-Carboxylic Acid Derivatives as Potent SIRT3 Inhibitors |
| title_fullStr | Discovery of 2-(4-Acrylamidophenyl)-Quinoline-4-Carboxylic Acid Derivatives as Potent SIRT3 Inhibitors |
| title_full_unstemmed | Discovery of 2-(4-Acrylamidophenyl)-Quinoline-4-Carboxylic Acid Derivatives as Potent SIRT3 Inhibitors |
| title_short | Discovery of 2-(4-Acrylamidophenyl)-Quinoline-4-Carboxylic Acid Derivatives as Potent SIRT3 Inhibitors |
| title_sort | discovery of 2 4 acrylamidophenyl quinoline 4 carboxylic acid derivatives as potent sirt3 inhibitors |
| topic | SIRT3 selective inhibitor mixed-lineage leukemias cell cycle arrest differentiation |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.880067/full |
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