Abstract：
A chemical fingerprinting approach utilizing LC-MS/MS coupled with 2D NMR data was established to characterize the profile of sorbicilinoid-type metabolites from a deep-sea derived fungus Penicillium rubens F54. Targeted isolation of the cultured fungus resulted in the discovery of 11 undescribed sorbicilinoids namely sorbicillinolides A-K (1-11). Their structures were identified by extensive analyses of the spectroscopic data, including the calculation of electronic circular dichroism and optical rotation for configurational assignments. The cyclopentenone core of sorbicillinolides A-D is likely derived from sorbicillin/dihydrosorbicillin through a newly oxidative rearrangement. The stereoisomers of sorbicillinolides E-G incorporate a nitrogen unit, forming a unique hydroquinoline nucleus. Sorbicillinolides A and C exhibited significant anti-neuroinflammation in LPS-stimulated BV-2 macrophages, achieved by potent inhibition of NO and PGE2 production through the interruption of RNA transcription of iNOS, COX-2 and IL6 in the NF-κB signaling pathway. Further investigation identified COX-2 as a potential target of sorbicillinolide A. These findings suggest sorbicillinolide A as a potential lead for the development of a non-steroidal anti-neuroinflammatory agent.
摘要：
建立了一种利用LC-MS/MS结合2DNMR数据的化学指纹图谱方法，以表征来自深海真菌红青霉F54的山梨醇类代谢物的特征。有针对性地分离培养的真菌导致发现了11种未描述的山梨素类化合物，即山梨素内酯A-K（1-11）。通过对光谱数据的广泛分析确定了它们的结构，包括电子圆二色性和旋光性的配置分配的计算。山梨糖醇内酯A-D的环戊烯酮核可能通过新的氧化重排衍生自山梨糖醇/二氢山梨糖醇。山梨糖醇内酯E-G的立体异构体引入了一个氮单元，形成独特的氢喹啉核。山梨糖醇内酯A和C在LPS刺激的BV-2巨噬细胞中表现出明显的抗神经炎症，通过中断iNOS的RNA转录来有效抑制NO和PGE2的产生，NF-κB信号通路中的COX-2和IL6.进一步的研究将COX-2确定为山梨素内酯A的潜在靶标。这些发现表明山梨素内酯A是开发非甾体类抗神经炎药的潜在先导物。
