目的 研究海绵共附生青霉Penicillium sp. LHW5975的化学成分。方法 采用减压硅胶柱色谱、十八烷基硅烷键合硅胶填料（ODS）中压柱色谱和半制备高效液相色谱等技术进行分离纯化，得到的单体化合物通过高分辨-电喷雾-质谱（HR-ESI-MS）、核磁共振波谱（NMR）以及与文献比对等方法进行鉴定。对分离得到的化合物进行斑马鱼促血管生成活性评价。结果 从Penicillium sp. LHW5975中分离纯化出9个生物碱类化合物，包括1个新的化合物，命名为青霉吲哚碱甲（1）；以及8个已知化合物，分别为17-羟基短密青霉酰胺N（2）、苯并玛尔维碱A（3）、苯并玛尔维碱B（4）、苯并玛尔维碱C（5）、苯并玛尔维碱D（6）、苯并玛尔维碱E（7）、(−)-苯并玛尔维碱E（8）和N-甲基诺喔苯并玛尔维碱A（9）。化合物2和7在50 µg/mL质量浓度下对斑马鱼节间血管的生长有促进作用。结论 化合物1为新化合物，化合物2和9为青霉属内首分化合物，化合物2和7具有一定的促血管生成活性。

Objective To reveal the secondary metabolites of the fermentation of marine sponge associated Penicillium sp. LHW5975. Methods The organic extract and fractions were separated and purified by silica vacuum liquid chromatography (VLC), octadecylsilyl silica (ODS) medium-pressure column chromatography (MPLC) and semi-preparative high-performance liquid chromatography (HPLC). The obtained purified compounds were identified by high-resolution-electrospray-mass spectrometry (HR-ESI-MS), nuclear magnetic resonance spectroscopy (NMR) and literature data comparison. Results Nine compounds were isolated from Penicillium sp. LHW5975, including one new compound penicindoline A (1) and eight known compounds, which are 17-hydroxybrevianamide N (2), benzomalvin A (3), benzomalvin B (4), benzomalvin C (5), benzomalvin D (6), benzomalvin E (7), (−)-benzomalvin E (8), and N-methylnovobenzomalvin A (9). Proangiogenesis activity evaluation of the isolated compounds using zebra fish model showed that benzodiazepines 2 and 7 promoted the angiogenesis at the concentration of 50 µg/mL. Conclusion Compound 1 is a new compound, and compound 2 and 9 are isolated from Penicillium sp. for the first time. Compound 2 and 7 have proangiogenesis activity.

R284.1

国家重点研发计划项目（2022YFC2804100）；国家自然科学基金项目（82022068）；国家自然科学基金项目（22137006）