Suberoylanilide Hydroxamic Acid, a Histone Deacetylase Inhibitor, Induces the Production of Anti-inflammatory Cyclodepsipeptides from Beauveria felina

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• 作者：Yu-Ming Chung ; Mohamed El-Shazly ; Da-Wei Chuang ; Tsong-Long Hwang ; Teigo Asai ; Yoshiteru Oshima ; Mohamed L. Ashour ; Yang-Chang Wu ; Fang-Rong Chang
• 刊名：Journal of Natural Products
• 出版年：2013
• 出版时间：July 26, 2013
• 年：2013
• 卷：76
• 期：7
• 页码：1260-1266
• 全文大小：353K
• 年卷期：v.76,no.7(July 26, 2013)
• ISSN：1520-6025

文摘

The addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid to a culture of the filamentous fungus Beauveria felina significantly changed its secondary metabolite profile and led to the isolation of eight compounds, including three new cyclodepsipeptides, desmethylisaridin E (1), desmethylisaridin C2 (2), and isaridin F (3), along with five known cyclodepsipeptide compounds. Isaridin F (3) possesses a cyclodepsipeptide ring with N-methylbutyric acid, which is rare in natural peptides. Absolute configurations of the new cyclodepsipeptides were achieved by Marfey鈥檚 method. The anti-inflammatory activity of the isolated compounds was investigated through evaluating their effect on superoxide anion production and elastase release by FMLP-induced human neutrophils. Among the tested compounds, desmethylisaridin E (1) inhibited superoxide anion production and desmethylisaridin C2 (2) inhibited elastase release, with IC₅₀ values of 10.00 卤 0.80 and 10.01 卤 0.46 渭M, respectively.