Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
School of Biological Sciences, University of Utah, Salt Lake City, Utah 84112, United States.
J Nat Prod. 2020 Apr 24;83(4):1249-1257. doi: 10.1021/acs.jnatprod.0c00038. Epub 2020 Mar 18.
Calcium homeostasis is implicated in some cancers, leading to the possibility that selective control of calcium might lead to new cancer drugs. On the basis of this idea, we designed an assay using a glioblastoma cell line and screened a collection of 1000 unique bacterial extracts. Isolation of the active compound from a hit extract led to the identification of boholamide A (), a 4-amido-2,4-pentadieneoate (APD)-class peptide. Boholamide A () applied in the nanomolar range induces an immediate influx of Ca in glioblastoma and neuronal cells. APD-class natural products are hypoxia-selective cytotoxins that primarily target mitochondria. Like other APD-containing compounds, is hypoxia selective. Since APD natural products have received significant interest as potential chemotherapeutic agents, provides a novel APD scaffold for the development of new anticancer compounds.
钙稳态与一些癌症有关，这使得选择性控制钙的可能性成为开发新型癌症药物的途径。基于这一想法，我们设计了一种使用神经胶质瘤细胞系的测定方法，并筛选了 1000 种独特的细菌提取物。从命中提取物中分离活性化合物导致鉴定出了 boholamide A（），一种 4-酰胺-2,4-戊二烯酸酯（APD）类肽。在纳摩尔范围内应用 boholamide A（）可立即诱导神经胶质瘤和神经元细胞内 Ca 的流入。APD 类天然产物是缺氧选择性细胞毒素，主要靶向线粒体。与其他含 APD 的化合物一样，是缺氧选择性的。由于 APD 天然产物作为潜在化疗药物受到了广泛关注，因此为开发新型抗癌化合物提供了一种新型 APD 支架。
