Angiogenesis Inhibitors and Anti-Inflammatory Agents from Phoma sp. NTOU4195

• Published in: Journal of natural products (Washington, D.C.) Vol. 79; no. 12; pp. 2983 - 2990
• Main Authors: Lee, Ming-Shian, Wang, Shih-Wei, Wang, Guei-Jane, Pang, Ka-Lai, Lee, Ching-Kuo, Kuo, Yueh-Hsiung, Cha, Hyo-Jung, Lin, Ruo-Kai, Lee, Tzong-Huei
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 23.12.2016; Amer Chemical Soc
• Subjects: Angiogenesis Inhibitors - chemistry; Angiogenesis Inhibitors - isolation & purification; Angiogenesis Inhibitors - pharmacology; Animals; Anti-Inflammatory Agents - chemistry; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Ascomycota - chemistry; Chemistry, Medicinal; Epoxy Compounds - pharmacology; Humans; Life Sciences & Biomedicine; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Marine Biology; Mice; Molecular Structure; Nitric Oxide - biosynthesis; Pharmacology & Pharmacy; Plant Sciences; Polyketides - chemistry; Polyketides - isolation & purification; Polyketides - pharmacology; Science & Technology; Spiro Compounds - pharmacology; Taiwan; PSEUROTIN-A; CELLS; ASPERGILLUS-FUMIGATUS; ABSOLUTE-CONFIGURATION; PSEUDEUROTIUM-OVALIS STOLK; FD-838; METABOLITE
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.6b00407

Seven new polyketides, phomaketides A–E (1–5) and pseurotins A3 (6) and G (7), along with the known compounds FR-111142, pseurotins A, A1, A2, D, and F2, 14-norpseurotin A, α-carbonylcarbene, tyrosol, cyclo­(-l-Pro-l-Leu), and cyclo­(-l-Pro-l-Phe), were purified from the fermentation broth and mycelium of the endophytic fungal strain Phoma sp. NTOU4195 isolated from the marine red alga Pterocladiella capillacea. The structures were established through interpretation of spectroscopic data. The antiangiogenic and anti-inflammatory effects of 1–7 and related analogues were evaluated using human endothelial progenitor cells (EPCs) and lipopolysaccharide (LPS)-activated murine macrophage RAW264.7 cells, respectively. Of the compounds tested, compound 1 exhibited the most potent antiangiogenic activity by suppressing the tube formation of EPCs with an IC50 of 8.1 μM, and compound 3 showed the most selective inhibitory activity of LPS-induced NO production in RAW264.7 macrophages with an IC50 value of 8.8 μM.