Angiogenesis Inhibitors and Anti-Inflammatory Agents from Phoma sp NTOU4195

Angiogenesis Inhibitors and Anti-Inflammatory Agents from Phoma sp NTOU4195
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DOI:
10.1021/acs.jnatprod.6b00407
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发表时间:
2016-12-01
影响因子:
5.1
通讯作者:
Lee, Tzong-Huei
Lee, Tzong-Huei
中科院分区:
生物学2区
文献类型:
--
作者:
Lee, Ming-Shian;Wang, Shih-Wei;Lee, Tzong-Huei

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7种新的聚酮化合物,phomaketides A-E(1-5)和pseudotins A(3)(6)和G(7),沿着已知化合物FR-111142,pseudotins A,A(1),A(2),D和F-2,14-norpseurotin A,α-carbonylcarbene,tyrosol,cyclo从海洋红藻Pterocladiella capillacea的内生真菌Phoma sp. NTOU 4195的发酵液和菌丝体中分离纯化了胞苷(-L-Pro-L-Leu)和胞苷(-L-Pro-L-Phe)。通过光谱数据的解释确定了结构。分别使用人内皮祖细胞(EPCs)和脂多糖(LPS)活化的鼠巨噬细胞RAW 264.7细胞评价1-7和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通过抑制EPC的管形成而显示出最有效的抗血管生成活性,其IC 50为8.1 μ M,化合物3显示出对RAW 264.7巨噬细胞中LPS诱导的NO产生的最选择性抑制活性,其IC 50值为8.8 μ M。
Seven new polyketides, phomaketides A-E (1-5) and pseurotins A(3) (6) and G (7), along with the known compounds FR-111142, pseurotins A, A(1), A(2), D, and F-2, 14-norpseurotin A, alpha-carbonylcarbene, tyrosol, cyclo(-L-Pro-L-Leu), and cydo(-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 mu M, 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 mu M.