Design, synthesis and antitumor activity of 3,4,5-Trisubstituted Isoxazoles

European Journal of Medicinal Chemistry Reports Pub Date : 2024-08-19 DOI:10.1016/j.ejmcr.2024.100203

Kanghui Duan , Fuxing Tan , Hongming Xie , Haiwang Liu , Yingjun Zhang , Huanfeng Jiang , Wanqing Wu

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Abstract

In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxicity against nine cancer cells. Among them, compound 14–3 has an IC₅₀ of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer. In addition, 14–3 induces apoptosis and leads to cell cycle arrest in the G2/M phase. Cytotoxicity tests on human normal hepatocytes LO2 also demonstrates that 14–3 is less toxic than 5-Fu with no obvious toxicity. These results suggest that 14–3 is a potential candidate for the development of anti-tumor drugs.

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3,4,5-三取代异噁唑的设计、合成和抗肿瘤活性

本研究合成了 56 种异噁唑衍生物，并检测了它们对 BXPC-3、MiaPaCa-2、PANC-1、MCF-7、HCT-116、HepG2、NCI-H460、A549 和 B16 等 9 种癌细胞的抗肿瘤活性。药理实验结果表明，大多数化合物对九种癌细胞具有良好的细胞毒性。其中，化合物 14-3 对结肠癌细胞 HCT-116 的 IC50 为 2.4 μM，效果最好，优于治疗结肠癌的广谱药物 5-氟尿嘧啶（5-Fu）。此外，14-3 还能诱导细胞凋亡，并导致细胞周期停滞在 G2/M 期。对人类正常肝细胞 LO2 的细胞毒性测试也表明，14-3 的毒性低于 5-Fu，且无明显毒性。这些结果表明，14-3 是一种潜在的候选抗肿瘤药物。

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来源期刊

European Journal of Medicinal Chemistry Reports

CiteScore

4.50

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0.00%

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