Development of Hypoxia-Inducible Factor (HIF)-1α Inhibitors: Effect of ortho-Carborane Substituents on HIF Transcriptional -Activity under Hypoxia 23, 1455-1461 (2013).
Development of Hypoxia-Inducible Factor (HIF)-1α Inhibitors: Effect of ortho-Carborane Substituents on HIF Transcriptional -Activity under Hypoxia 23, 1455-1461 (2013).
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缺氧诱导因子(HIF)-1α抑制剂的开发：邻碳硼烷取代基对缺氧下HIF转录活性的影响23, 1455-1461 (2013)。
DOI：
10.1016/j.bmcl.2012.11.081
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
S. Sato,
中科院分区：
文献类型：
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作者：
H. Nakamura;Y. Yasui;M. Maruyama;H. Minegishi;H. S. Ban;S. Sato,
合成了一系列取代的邻碳硼烷基苯氧基乙酰苯胺，并在表达 HRE 依赖性萤火虫荧光素酶报告基因构建体 (HRE-Luc) 和组成型表达 CMV 驱动的海肾荧光素酶报告基因的 HeLa 细胞中使用基于细胞的报告基因测定评估了它们抑制缺氧诱导的 HIF-1 转录活性的能力，并使用 MTT 测定评估了它们抑制细胞生长 (GI50) 的能力。在合成的化合物中，1g和1l对缺氧诱导的HIF-1转录活性具有显着抑制作用（IC50分别为1.9±0.4和1.4±0.2μM）。两种化合物均以浓度依赖性方式抑制 HIF-1α 积累。猪心苹果酸脱氢酶(MDH)重折叠实验表明，化合物1l抑制人Hsp60分子伴侣活性(IC50：6.80±0.25μM)，且抑制活性高于ETB(IC50：10.9±0.63μM)。
A series of substituted ortho-carboranylphenoxyacetanilides were synthesized and evaluated for their ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell-based reporter assay in HeLa cells expressing the HRE-dependent firefly luciferase reporter construct (HRE-Luc) and constitutively expressing CMV-driven Renilla luciferase reporter, and their ability to inhibit cell growth (GI50) using the MTT assay. Among the compounds synthesized, 1g and 1l showed significant inhibition of hypoxia-induced HIF-1 transcriptional activity (IC50: 1.9±0.4 and 1.4±0.2μM, respectively). Both compounds suppressed HIF-1α accumulation in a concentration-dependent manner. The porcine heart malate dehydrogenase (MDH) refolding assay revealed that compound 1l inhibited human Hsp60 chaperone activity (IC50: 6.80±0.25μM) and this inhibition activity was higher than that of ETB (IC50: 10.9±0.63μM).