Discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 (STAT3)
Gastric cancer remains a significant health burden worldwide. In continuation of our previous study and development of effective small molecules against gastric cancer, a series of benzochalcone analogues involving heterocyclic molecules were synthesised and biologically evaluated in vitro and in vi...
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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/10.1080/14756366.2022.2100366 |
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| author | Jinyun Dong Jing Yang Wenkai Yu Haobin Li Maohua Cai Jing-Li Xu Han-Dong Xu Yun-Fu Shi Xiaoqing Guan Xiang‑Dong Cheng Jiang‑Jiang Qin |
| author_facet | Jinyun Dong Jing Yang Wenkai Yu Haobin Li Maohua Cai Jing-Li Xu Han-Dong Xu Yun-Fu Shi Xiaoqing Guan Xiang‑Dong Cheng Jiang‑Jiang Qin |
| author_sort | Jinyun Dong |
| collection | DOAJ |
| description | Gastric cancer remains a significant health burden worldwide. In continuation of our previous study and development of effective small molecules against gastric cancer, a series of benzochalcone analogues involving heterocyclic molecules were synthesised and biologically evaluated in vitro and in vivo. Among them, the quinolin-6-yl substituted derivative KL-6 inhibited the growth of gastric cancer cells (HGC27, MKN28, AZ521, AGS, and MKN1) with a submicromolar to micromolar range of IC50, being the most potent one in this series. Additionally, KL-6 significantly inhibited the colony formation, migration and invasion, and effectively induced apoptosis of MKN1 cells in a concentration-dependent manner. The mechanistic study revealed that KL-6 could concentration-dependently suppress STAT3 phosphorylation, which may partly contribute to its anticancer activity. Furthermore, in vivo antitumour study on the MKN1 orthotopic tumour model showed that KL-6 effectively inhibited tumour growth (TGI of 78%) and metastasis without obvious toxicity. Collectively, compound KL-6 may support the further development of candidates for gastric cancer treatment. |
| format | Article |
| id | doaj-art-59f779a14cb74fd68b924c8ac81f8a4e |
| 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-59f779a14cb74fd68b924c8ac81f8a4e2025-08-20T03:31:27ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742022-12-013712004201610.1080/14756366.2022.2100366Discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 (STAT3)Jinyun Dong0Jing Yang1Wenkai Yu2Haobin Li3Maohua Cai4Jing-Li Xu5Han-Dong Xu6Yun-Fu Shi7Xiaoqing Guan8Xiang‑Dong Cheng9Jiang‑Jiang Qin10The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaSchool of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, ChinaThe First Clinical Medical College of Zhejiang, Chinese Medical University, Hangzhou, ChinaThe First Clinical Medical College of Zhejiang, Chinese Medical University, Hangzhou, ChinaThe First Clinical Medical College of Zhejiang, Chinese Medical University, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaThe Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, ChinaGastric cancer remains a significant health burden worldwide. In continuation of our previous study and development of effective small molecules against gastric cancer, a series of benzochalcone analogues involving heterocyclic molecules were synthesised and biologically evaluated in vitro and in vivo. Among them, the quinolin-6-yl substituted derivative KL-6 inhibited the growth of gastric cancer cells (HGC27, MKN28, AZ521, AGS, and MKN1) with a submicromolar to micromolar range of IC50, being the most potent one in this series. Additionally, KL-6 significantly inhibited the colony formation, migration and invasion, and effectively induced apoptosis of MKN1 cells in a concentration-dependent manner. The mechanistic study revealed that KL-6 could concentration-dependently suppress STAT3 phosphorylation, which may partly contribute to its anticancer activity. Furthermore, in vivo antitumour study on the MKN1 orthotopic tumour model showed that KL-6 effectively inhibited tumour growth (TGI of 78%) and metastasis without obvious toxicity. Collectively, compound KL-6 may support the further development of candidates for gastric cancer treatment.https://www.tandfonline.com/doi/10.1080/14756366.2022.2100366Benzochalcone analoguesSTAT3gastric cancer |
| spellingShingle | Jinyun Dong Jing Yang Wenkai Yu Haobin Li Maohua Cai Jing-Li Xu Han-Dong Xu Yun-Fu Shi Xiaoqing Guan Xiang‑Dong Cheng Jiang‑Jiang Qin Discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 (STAT3) Journal of Enzyme Inhibition and Medicinal Chemistry Benzochalcone analogues STAT3 gastric cancer |
| title | Discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 (STAT3) |
| title_full | Discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 (STAT3) |
| title_fullStr | Discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 (STAT3) |
| title_full_unstemmed | Discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 (STAT3) |
| title_short | Discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 (STAT3) |
| title_sort | discovery of benzochalcone derivative as a potential antigastric cancer agent targeting signal transducer and activator of transcription 3 stat3 |
| topic | Benzochalcone analogues STAT3 gastric cancer |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2022.2100366 |
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