Abstract：
Seven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine phosphatase 1B (PTP1B) with IC50 value of 8.60 ± 0.53 μM. Compound 17 showed significant α-glucosidase inhibitory activity with IC50 value of 19.96 ± 0.32 μM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages.
摘要：
七种新吲哚二萜，阴茎A-E（1-5），7-甲氧基吡嗪-13-烯（6），和10-羟基-帕斯帕林(7)，连同20个已知的(8-27)，是从海洋真菌青霉中分离出来的。ZYX-Z-143.其中,化合物1是带有2,3,3a的螺吲哚二萜，5-四氢-1H-苯并[d]吡咯并[2,1-b][1,3]恶嗪-1-酮基序。化合物2的特征在于具有罕见的3,6,8-三氧双环[3.2.1]辛烷单元的独特七环系统。通过广泛的光谱分析确定了新化合物的结构，NMR计算与DP4+分析相结合，和ECD计算。两种前所未有的吲哚二萜的合理生物遗传途径，笔状突起A和B（1和2），被假定。化合物1用作针对蛋白酪氨酸磷酸酶1B(PTP1B)的非竞争性抑制剂,IC50值为8.60±0.53μM。化合物17显示显著的α-葡萄糖苷酶抑制活性,IC50值为19.96±0.32μM。此外，化合物4,8和22能有效抑制脂多糖刺激的RAW264.7巨噬细胞产生一氧化氮.
