| 引用本文: | 刘瑶,李珊,裘旎,胡永洲,曹戟,盛荣.3-芳基-5-三氮唑基-噁二唑衍生物HIF-1抑制剂的设计、合成与构效关系研究[J].中国现代应用药学,2022,39(5):573-583. |
| LIU Yao,LI Shan,QIU Ni,HU Yongzhou,CAO Ji,SHENG Rong.Design, Synthesis and Structure-activity Relationship Study of 3-Aryl-5-triazolyl-oxadiazole Derivatives as Hypoxia-inducible Factor-1 Inhibitors[J].Chin J Mod Appl Pharm(中国现代应用药学),2022,39(5):573-583. |
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| 摘要: |
| 目的 设计、合成3-芳基-5-三氮唑基-噁二唑类缺氧诱导因子-1(hypoxia-inducible factor 1，HIF-1)抑制剂。方法 以化合物8为先导，将吡唑基替换为1,2,3-三氮唑基，并对噁二唑和苯环取代基等进行改造，获得全新的3-芳基-5-三氮唑基-噁二唑衍生物。结果 所合成的大部分化合物均显示出较优的HIF-1抑制活性，化合物10n活性最强，IC50值为0.59 μmol·L-1，其作用机制是抑制HIF-1α蛋白表达，且能显著抑制SKOV3细胞的侵袭和迁移。结论 设计、合成的3-芳基-5-三氮唑基-噁二唑类衍生物是全新的HIF-1抑制剂，显示出抑制肿瘤迁移的效应。 |
| 关键词: 缺氧诱导因子-1 抑制剂 3-芳基-5-三氮唑基-噁二唑衍生物 构效关系 肿瘤转移 |
| DOI：10.13748/j.cnki.issn1007-7693.2022.05.001 |
| 分类号:R914.4 |
| 基金项目:国家自然科学基金项目（21672187）；浙江省自然科学基金项目（LZ17H300002） |
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| Design, Synthesis and Structure-activity Relationship Study of 3-Aryl-5-triazolyl-oxadiazole Derivatives as Hypoxia-inducible Factor-1 Inhibitors |
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LIU Yao, LI Shan, QIU Ni, HU Yongzhou, CAO Ji, SHENG Rong
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College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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| Abstract: |
| OBJECTIVE To design and synthesize a series of 3-aryl-5-triazolyl-oxadiazole derivatives as hypoxia- inducible factor 1(HIF-1) inhibitors. METHODS Taking compound 8 as the guide, the pyrazolyl group was replaced with 1,2,3-triazole group, and the oxadiazole and benzene ring substituents were modified to obtain a novel series of 3-aryl-5-triazole group oxadiazole derivatives. RESULTS Most of these newly designed compounds showed good HIF-1 inhibitory activities and compound 10n was the most potent inhibitor with IC50 value of 0.59 μmol·L-1. Its mechanism of action was to inhibit the expression of HIF-1α protein, and could significantly inhibit the invasion and migration of SKOV3 cells. CONCLUSION The series of 3-aryl-5-triazolyl-oxadiazole derivatives are new HIF-1 inhibitors, showing the effect of inhibiting tumor migration. |
| Key words: HIF-1 inhibitor 3-aryl-5-triazolyl-oxadiazoles derivatives structure-activity relationship tumor metastasis |
