A Potent HDAC Inhibitor, 1-Alaninechlamydocin, from a Tolypocladium sp. Induces G2/M Cell Cycle Arrest and Apoptosis in MIA PaCa-2 Cells

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• 作者：Lin Du ; April L. Risinger ; Jarrod B. King ; Douglas R. Powell ; Robert H. Cichewicz
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：July 25, 2014
• 年：2014
• 卷：77
• 期：7
• 页码：1753-1757
• 全文大小：324K
• ISSN：1520-6025

文摘

The cyclic tetrapeptide 1-alaninechlamydocin was purified from a Great Lakes-derived fungal isolate identified as a Tolypocladium sp. Although the planar structure was previously described, a detailed analysis of its spectroscopic data and biological activity are reported here for the first time. Its absolute configuration was determined using a combination of spectroscopic (¹H鈥?sup>1H ROESY, ECD, and X-ray diffraction) and chemical (Marfey鈥檚 analysis) methods. 1-Alaninechlamydocin showed potent antiproliferative/cytotoxic activities in a human pancreatic cancer cell line (MIA PaCa-2) at low-nanomolar concentrations (GI₅₀ 5.3 nM, TGI 8.8 nM, LC₅₀ 22 nM). Further analysis revealed that 1-alaninechlamydocin induced G2/M cell cycle arrest and apoptosis. Similar to other cyclic epoxytetrapeptides, the inhibitory effects of 1-alaninechlamydocin are proposed to be produced primarily via inhibition of histone deacetylase (HDAC) activity.