Phoma sp. NTOU4195 来源的血管生成抑制剂和抗炎剂。

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

机构信息

Department of Medicine, Mackay Medical College , New Taipei City 25245, Taiwan.

School of Medicine, Graduate Institute of Clinical Medical Science, China Medical University , Taichung 40402, Taiwan.

出版信息

J Nat Prod. 2016 Dec 23;79(12):2983-2990. doi: 10.1021/acs.jnatprod.6b00407. Epub 2016 Dec 15.

DOI:10.1021/acs.jnatprod.6b00407

PMID:27976895

Abstract

Seven new polyketides, phomaketides A-E (1-5) and pseurotins A (6) and G (7), along with the known compounds FR-111142, pseurotins A, A, A, D, and F, 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 IC of 8.1 μM, and compound 3 showed the most selective inhibitory activity of LPS-induced NO production in RAW264.7 macrophages with an IC value of 8.8 μM.

摘要

从海洋红藻 Pterocladiella capillacea 内生真菌 Phoma sp. NTOU4195 的发酵液和菌丝体中分离得到了 7 种新的聚酮化合物，phomaketides A-E（1-5）和 pseurotins A（6）和 G（7），以及已知的化合物 FR-111142、pseurotins A、A、A、D 和 F、14-norpseurotin A、α-羰基卡宾、酪氨酸、环(-l-Pro-l-Leu)和环(-l-Pro-l-Phe)。通过解析光谱数据确定了它们的结构。采用人内皮祖细胞（EPC）和脂多糖（LPS）激活的小鼠巨噬细胞 RAW264.7 细胞分别评估了 1-7 及其相关类似物的抗血管生成和抗炎作用。在所测试的化合物中，化合物 1 表现出最强的抗血管生成活性，抑制 EPC 管形成的 IC 为 8.1 μM，化合物 3 对 LPS 诱导的 RAW264.7 巨噬细胞中 NO 产生的抑制活性最具选择性，IC 值为 8.8 μM。