Diaporindenes A-D: Four Unusual 2,3-Dihydro-1 H-indene Analogues with Anti-inflammatory Activities from the Mangrove Endophytic Fungus Diaporthe sp. SYSU-HQ3

• Published in: Journal of organic chemistry 2018-10, Vol.83 (19), p.11804-11813
• Main Authors: Cui, Hui, Liu, Yena, Li, Jing, Huang, Xishan, Yan, Tao, Cao, Wenhao, Liu, Hongju, Long, Yuhua, She, Zhigang
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Ascomycota - chemistry; Endophytes - chemistry; Indenes - chemistry; Indenes - pharmacology; Mice; Models, Molecular; Molecular Conformation; Nitric Oxide - biosynthesis; RAW 264.7 Cells
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.8b01738

Diaporindenes A-D (1-4), four unusual 2,3-dihydro-1 H-indene isomers, a novel isoprenylisobenzofuran A (5), two new isoprenylisoindole alkaloids diaporisoindoles D and E (6 and 7), and a new benzophenone derivative tenellone D (11), together with four known biogenetic agents (8-10 and 12), were all separated from the endophytic fungus Diaporthe sp. SYSU-HQ3 guided by ultraperformance liquid chromatography high-resolution mass spectrometry. The absolute configurations of 1-7 and 11 were defined by X-ray diffraction, quantum chemical calculations, and spectroscopic analysis. Diaporindenes A-D (1-4) possessed an unprecedented chemical skeleton featuring a 2,3-dihydro-1 H-indene ring and a 1,4-benzodioxan moiety. All of the isolates (1-12) were tested for their inhibitory effects on the production of nitric oxide in lipopolysaccharide-induced microglial cells (RAW 264.7 cells). Compounds 1-5, 8, and 9 were found to exhibit significant inhibitory effects against nitric oxide production with IC values from 4.2 to 9.0 μM and SI values from 3.5 to 6.9. In addition, the structure-activity relationships of all compounds were summarized.