Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA.
J Nat Prod. 2013 Jun 28;76(6):1175-81. doi: 10.1021/np400320r. Epub 2013 Jun 3.
The hypoxia-inducible factor-1 (HIF-1) transcription factor regulates cellular oxygen homeostasis. Agents that activate HIF-1 and downstream HIF targets represent potential drug leads for the prevention and/or treatment of ischemic disorders. In a search for small-molecule HIF-1 activators, 1936 marine invertebrate and algal extract samples (U.S. National Cancer Institute's Open Repository) were evaluated for HIF-1 activation activity in a cell-based reporter assay. Bioassay-guided fractionation of two active extracts of the sponge Dactylospongia elegans afforded four new sesquiterpene quinones (2-5), one new sesquiterpene phenol (6), the known Golgi disruptor ilimaquinone (1), and three previously reported ilimaquinone analogues (7-9). While antiproliferative activity was observed at higher concentrations, the sesquiterpene quinones (1-3) possessing a 2-hydroxy-5-methoxy-1,4-benzoquinone moiety activated HIF-1 and increased the expression of HIF-1 target gene vascular endothelial growth factor (VEGF) in T47D cells.
缺氧诱导因子-1 (HIF-1) 转录因子调节细胞的氧稳态。激活 HIF-1 和下游 HIF 靶标的药物代表了预防和/或治疗缺血性疾病的潜在药物先导物。在寻找小分子 HIF-1 激活剂的过程中，1936 种海洋无脊椎动物和藻类提取物样本（美国国家癌症研究所开放资源库）在基于细胞的报告基因测定中评估了 HIF-1 激活活性。海绵 Dactylospongia elegans 的两个活性提取物的生物活性指导分离得到了四个新的倍半萜醌（2-5）、一个新的倍半萜酚（6）、已知的高尔基破坏剂伊莱马醌（1）和三个以前报道的伊莱马醌类似物（7-9）。虽然在较高浓度下观察到抗增殖活性，但具有 2-羟基-5-甲氧基-1,4-苯醌部分的倍半萜醌（1-3）激活了 HIF-1，并增加了 T47D 细胞中 HIF-1 靶基因血管内皮生长因子 (VEGF) 的表达。
