紅藻源真菌株 Aspergillus unguis NTU142之活性成分研究

Abstract

本研究利用抑制革蘭氏陽性金黃色葡萄球菌 (Staphylococcus aureus) 之活性為篩選平台，發現長沙枝菜 (Hypnea Charoides) 之衍生真菌株Aspergillus unguis NTU142的MY (malt extract, yeast extract) 醱酵培養液具顯著的抑菌活性。接著以MY (malt extract, yeast extract) 液態培養基加以擴大培養，針對其醱酵液所含代謝產物進行分析、分離與純化，共計獲得13個化合物，藉由各種光譜分析決定其結構。其中4個新化合物，包括：unguistin A (1)、unguistin B (2)、unguisine A (3) 和unguisine B (4)，另外為9個為已知化合物unguinol (5)、aspergillusidone A (6)、2-chlorounguinol (7)、aspergillusidone C (8)、agonodepside A (9)、7-chlorofolipastatin (10)、nornidulin (11)、pilobolusate (12) 和2,4-dichlorounguinol (13)。各化合物進行抑菌活性評估，得知agonodepside A (9) 和7-chlorofolipastatin (10) 對金黃色葡萄球菌 (Staphylococcus aureus) 與其他化合物相比有最佳的抑菌活性，其最小抑菌濃度 (MIC) 皆為4 μg/ml。在抑制 BV-2 細胞的生成一氧化氮上，aspergillusidone A (6) 有顯著的效果，其半抑制濃度 (IC50) 為 5.1 ± 1.6 μM。

Marine environment is one of the most important sources regarding natural product research. Besides, marine microorganisms have been denominated as talented natural sources for discovery of new leads. The target fungus, Aspergillus unguis NTU142, was isolated from a marine red alga Hypnea charoides, and was found to exhibit significant inhibitory activity against Staphylococcus aureus in our preliminary screening. Thus, a series of separation and purification of the active principles was undertaken. Thirteen compounds were isolated from large-scale fermentation broth of A. unguis NTU142, including four new unguistin A (1), unguistin B (2), unguisine A (3) and unguisine B (4), together with nine previously reported unguinol (5), aspergillusidone A (6), 2-chlorounguinol (7), aspergillusidone C (8), agonodepsides A (9), 7-chlorofolipastatin (10), nornidulin (11), pilobolusate (12) and 2,4-dichlorounguinol (13). Agonodepsides A (9) and 7-chlorofolipastatin (10) are likely responsible for the anti-microbial activity of the marine-derived A. unguis NTU142, which exhibited significant growth inhibition against S. aureus and C. neoformans. Aspergillusidone A (6) showed the most potent inhibitory effect on LPS-induced NO production in murine brain microglial BV-2 cells without cytotoxic activity.