Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives
The chalcone and quinoline scaffolds are frequently utilized to design novel anticancer agents. As the continuation of our work on effective anticancer agents, we assumed that linking chalcone fragment to the quinoline scaffold through the principle of molecular hybridization strategy could produce...
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MDPI AG
2021-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/16/4899 |
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| author | Yong-Feng Guan Xiu-Juan Liu Xin-Ying Yuan Wen-Bo Liu Yin-Ru Li Guang-Xi Yu Xin-Yi Tian Yan-Bing Zhang Jian Song Wen Li Sai-Yang Zhang |
| author_facet | Yong-Feng Guan Xiu-Juan Liu Xin-Ying Yuan Wen-Bo Liu Yin-Ru Li Guang-Xi Yu Xin-Yi Tian Yan-Bing Zhang Jian Song Wen Li Sai-Yang Zhang |
| author_sort | Yong-Feng Guan |
| collection | DOAJ |
| description | The chalcone and quinoline scaffolds are frequently utilized to design novel anticancer agents. As the continuation of our work on effective anticancer agents, we assumed that linking chalcone fragment to the quinoline scaffold through the principle of molecular hybridization strategy could produce novel compounds with potential anticancer activity. Therefore, quinoline-chalcone derivatives were designed and synthesized, and we explored their antiproliferative activity against MGC-803, HCT-116, and MCF-7 cells. Among these compounds, compound <b>12e</b> exhibited a most excellent inhibitory potency against MGC-803, HCT-116, and MCF-7 cells with IC<sub>50</sub> values of 1.38, 5.34, and 5.21 µM, respectively. The structure–activity relationship of quinoline-chalcone derivatives was preliminarily explored in this report. Further mechanism studies suggested that compound <b>12e</b> inhibited MGC-803 cells in a dose-dependent manner and the cell colony formation activity of MGC-803 cells, arrested MGC-803 cells at the G2/M phase and significantly upregulated the levels of apoptosis-related proteins (Caspase3/9 and cleaved-PARP) in MGC-803 cells. In addition, compound <b>12e</b> could significantly induce ROS generation, and was dependent on ROS production to exert inhibitory effects on gastric cancer cells. Taken together, all the results suggested that directly linking chalcone fragment to the quinoline scaffold could produce novel anticancer molecules, and compound <b>12e</b> might be a valuable lead compound for the development of anticancer agents. |
| first_indexed | 2024-03-10T08:32:57Z |
| format | Article |
| id | doaj.art-30cc84c1a9ea4e4ba893f04855a086f2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T08:32:57Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-30cc84c1a9ea4e4ba893f04855a086f22023-11-22T08:53:38ZengMDPI AGMolecules1420-30492021-08-012616489910.3390/molecules26164899Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone DerivativesYong-Feng Guan0Xiu-Juan Liu1Xin-Ying Yuan2Wen-Bo Liu3Yin-Ru Li4Guang-Xi Yu5Xin-Yi Tian6Yan-Bing Zhang7Jian Song8Wen Li9Sai-Yang Zhang10School of Chemical Engineering, Zhengzhou University, Zhengzhou 450001, ChinaKey Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaKey Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaKey Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaKey Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaKey Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Chemical Engineering, Zhengzhou University, Zhengzhou 450001, ChinaSchool of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaThe chalcone and quinoline scaffolds are frequently utilized to design novel anticancer agents. As the continuation of our work on effective anticancer agents, we assumed that linking chalcone fragment to the quinoline scaffold through the principle of molecular hybridization strategy could produce novel compounds with potential anticancer activity. Therefore, quinoline-chalcone derivatives were designed and synthesized, and we explored their antiproliferative activity against MGC-803, HCT-116, and MCF-7 cells. Among these compounds, compound <b>12e</b> exhibited a most excellent inhibitory potency against MGC-803, HCT-116, and MCF-7 cells with IC<sub>50</sub> values of 1.38, 5.34, and 5.21 µM, respectively. The structure–activity relationship of quinoline-chalcone derivatives was preliminarily explored in this report. Further mechanism studies suggested that compound <b>12e</b> inhibited MGC-803 cells in a dose-dependent manner and the cell colony formation activity of MGC-803 cells, arrested MGC-803 cells at the G2/M phase and significantly upregulated the levels of apoptosis-related proteins (Caspase3/9 and cleaved-PARP) in MGC-803 cells. In addition, compound <b>12e</b> could significantly induce ROS generation, and was dependent on ROS production to exert inhibitory effects on gastric cancer cells. Taken together, all the results suggested that directly linking chalcone fragment to the quinoline scaffold could produce novel anticancer molecules, and compound <b>12e</b> might be a valuable lead compound for the development of anticancer agents.https://www.mdpi.com/1420-3049/26/16/4899quinolinechalconeanticancer activitycell cycle arrestROS |
| spellingShingle | Yong-Feng Guan Xiu-Juan Liu Xin-Ying Yuan Wen-Bo Liu Yin-Ru Li Guang-Xi Yu Xin-Yi Tian Yan-Bing Zhang Jian Song Wen Li Sai-Yang Zhang Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives Molecules quinoline chalcone anticancer activity cell cycle arrest ROS |
| title | Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives |
| title_full | Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives |
| title_fullStr | Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives |
| title_full_unstemmed | Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives |
| title_short | Design, Synthesis, and Anticancer Activity Studies of Novel Quinoline-Chalcone Derivatives |
| title_sort | design synthesis and anticancer activity studies of novel quinoline chalcone derivatives |
| topic | quinoline chalcone anticancer activity cell cycle arrest ROS |
| url | https://www.mdpi.com/1420-3049/26/16/4899 |
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