*Article* **New Polyketides from Mangrove Endophytic Fungus** *Penicillium* **sp. BJR-P2 and Their Anti-Inflammatory Activity**

**Chen Chen, Geting Ye, Jing Tang, Jialin Li, Wenbin Liu, Li Wu and Yuhua Long \***

GDMPA Key Laboratory for Process Control and Quality Evaluation of Chiral Pharmaceuticals, Guangzhou Key Laboratory of Analytical Chemistry for Biomedicine, School of Chemistry, South China Normal University, Guangzhou 510006, China

**\*** Correspondence: longyh@scnu.edu.cn

**Abstract:** Four new polyketide compounds, including two new unique isocoumarins penicillol A (**1**) and penicillol B (**2**) featuring with spiroketal rings, two new citreoviridin derivatives citreoviridin H (**3**) and citreoviridin I (**4**), along with four known analogues were isolated from the mangrove endophytic fungus *Penicillium* sp. BJR-P2. Their structures were elucidated by extensive spectroscopic methods. The absolute configurations of compounds **1**–**4** based on electronic circular dichroism (ECD) calculations, DP4+ analysis, and single-crystal X-ray diffraction are presented. All the new compounds were evaluated for anti-inflammatory activity. An anti-inflammatory assay indicated that compound **2** inhibited lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values of 12 μM, being more potent than the positive control, indomethacin (IC50 = 35.8 ± 5.7 μM). Docking study showed that compound **2** was perfectly docking into the active site of murine inducible nitric oxide oxygenase (iNOS) via forming multiple typical hydrogen bonds.

**Keywords:** isocoumarins; polyketides; anti-inflammatory activity; *Penicillium* sp.
