喜马拉醌 A-G，由喜马拉雅分离株 sp. PU-MM59 产生的蒽环酮衍生代谢物。
Himalaquinones A-G, Angucyclinone-Derived Metabolites Produced by the Himalayan Isolate sp. PU-MM59.
机构信息
Department of Pharmacy, College of Life Sciences, China Jiliang University, Hangzhou 310018, People's Republic of China.
Institute of Microbiology and Molecular Genetics (MMG), University of the Punjab, Lahore 54590, Pakistan.
出版信息
J Nat Prod. 2021 Jul 23;84(7):1930-1940. doi: 10.1021/acs.jnatprod.1c00192. Epub 2021 Jun 25.
Himalaquinones A-G, seven new anthraquinone-derived metabolites, were obtained from the Himalayan-based sp. PU-MM59. The chemical structures of the new compounds were identified based on cumulative analyses of HRESIMS and NMR spectra. Himalaquinones A-F were determined to be unique anthraquinones that contained unusual C-4a 3-methylbut-3-enoic acid aromatic substitutions, while himalaquinone G was identified as a new 5,6-dihydrodiol-bearing angucyclinone. Comparative bioactivity assessment (antimicrobial, cancer cell line cytotoxicity, impact on 4E-BP1 phosphorylation, and effect on axolotl embryo tail regeneration) revealed cytotoxic landomycin and saquayamycin analogues to inhibit 4E-BP1p and inhibit regeneration. In contrast, himalaquinone G, while also cytotoxic and a regeneration inhibitor, did not affect 4E-BP1p status at the doses tested. As such, this work implicates a unique mechanism for himalaquinone G and possibly other 5,6-dihydrodiol-bearing angucyclinones.
希马拉醌 A-G，七种新的蒽醌衍生代谢产物，从喜马拉雅为基础的 种。PU-MM59 中获得。根据 HRESIMS 和 NMR 光谱的累积分析，确定了新化合物的化学结构。希马拉醌 A-F 被确定为具有独特的蒽醌，含有不寻常的 C-4a 3-甲基丁-3-烯酸芳香取代基，而希马拉醌 G 被鉴定为一种具有新的 5,6-二氢二醇的蒽环酮。比较生物活性评估（抗菌、癌细胞系细胞毒性、对 4E-BP1 磷酸化的影响和对蝾螈胚胎尾再生的影响）表明，细胞毒性的 landomycin 和 saquayamycin 类似物抑制 4E-BP1p 并抑制再生。相比之下，希马拉醌 G 虽然也具有细胞毒性和再生抑制剂的作用，但在测试剂量下不会影响 4E-BP1p 状态。因此，这项工作暗示了希马拉醌 G 可能还有其他具有 5,6-二氢二醇的蒽环酮的独特作用机制。
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