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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| Main Authors: | , , , , , , , , , , |
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| Format: | Book |
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Taylor & Francis Group,
2022-12-01T00:00:00Z.
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| Summary: | 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. |
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| Item Description: | 10.1080/14756366.2022.2100366 1475-6374 1475-6366 |