来源于夏威夷植物 Lycopodiella cernua 的真菌 Paraphaeosphaeria neglecta FT462 产生的具有硫化物和亚砜部分的独特 γ-吡喃醇-γ-内酰胺 NF-κB 抑制剂。
NF-κB inhibitors, unique γ-pyranol-γ-lactams with sulfide and sulfoxide moieties from Hawaiian plant Lycopodiella cernua derived fungus Paraphaeosphaeria neglecta FT462.
机构信息
Department of Pharmaceutical Sciences, Daniel K. Inouye College of Pharmacy, University of Hawai'i at Hilo, 200W. Kawili Street, Hilo, HI, 96720, USA.
Cancer Biology Program, Cancer Center, University of Hawaii, 701 Ilalo Street, Honolulu, Hawai'i, 96813, USA.
出版信息
Sci Rep. 2017 Sep 5;7(1):10424. doi: 10.1038/s41598-017-10537-1.
LC-UV/MS-based metabolomic analysis of the Hawaiian endophytic fungus Paraphaeosphaeria neglecta FT462 led to the identification of four unique mercaptolactated γ-pyranol-γ-lactams, paraphaeosphaerides E-H (1-4) together with one γ-lactone (5) and the methyl ester of compound 2 (11). The structures of the new compounds (1-5 and 11) were elucidated through the analysis of HRMS and NMR spectroscopic data. The absolute configuration was determined by chemical reactions with sodium borohydride, hydrogen peroxide, α-methoxy-α-(trifluoromethyl)phenylacetyl chlorides (Mosher reagents), and DP4 + NMR calculations. All the compounds were tested against STAT3, A2780 and A2780cisR cancer cell lines, E. coli JW2496, and NF-κB. Compounds 1 and 3 strongly inhibited NF-κB with IC values of 7.1 and 1.5 μM, respectively.
基于 LC-UV/MS 的夏威夷内生真菌 Paraphaeosphaeria neglecta FT462 的代谢组学分析，鉴定出四个独特的巯基内酯 γ-吡喃醇-γ-内酰胺，即 paraphaeosphaerides E-H（1-4），以及一个 γ-内酯（5）和化合物 2 的甲酯（11）。通过分析高分辨质谱和 NMR 波谱数据，阐明了新化合物（1-5 和 11）的结构。绝对构型通过与硼氢化钠、过氧化氢、α-甲氧基-α-（三氟甲基）苯乙酰氯（莫斯试剂）以及 DP4 + NMR 计算的化学反应来确定。所有化合物均针对 STAT3、A2780 和 A2780cisR 癌细胞系、E. coli JW2496 和 NF-κB 进行了测试。化合物 1 和 3 强烈抑制 NF-κB，IC 值分别为 7.1 和 1.5 μM。
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