Actinopolysporins A鈥揅 and Tubercidin as a Pdcd4 Stabilizer from the Halophilic Actinomycete Actinopolyspora erythraea YIM 90600

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• 作者：Li-Xing Zhao ; Sheng-Xiong Huang ; Shu-Kun Tang ; Cheng-Lin Jiang ; Yanwen Duan ; John A. Beutler ; Curtis J. Henrich ; James B. McMahon ; Tobias Schmid ; Johanna S. Blees ; Nancy H. Colburn ; Scott R. Rajski ; Ben Shen
• 刊名：Journal of Natural Products
• 出版年：2011
• 出版时间：September 23, 2011
• 年：2011
• 卷：74
• 期：9
• 页码：1990-1995
• 全文大小：781K
• 年卷期：v.74,no.9(September 23, 2011)
• ISSN：1520-6025

文摘

Our current natural product program utilizes new actinomycetes originating from unexplored and underexplored ecological niches, employing cytotoxicity against a selected panel of cancer cell lines as the preliminary screen to identify hit strains for natural product dereplication, followed by mechanism-based assays of the purified natural products to discover potential anticancer drug leads. Three new linear polyketides, actinopolysporins A (1), B (2), and C (3), along with the known antineoplastic antibiotic tubercidin (4), were isolated from the halophilic actinomycete Actinopolyspora erythraea YIM 90600, and the structures of the new compounds were elucidated on the basis of spectroscopic data interpretation. All four compounds were assayed for their ability to stabilize the tumor suppressor programmed cell death protein 4 (Pdcd4), which is known to antagonize critical events in oncogenic pathways. Only 4 significantly inhibited proteasomal degradation of a model Pdcd4鈥搇uciferase fusion protein, with an IC₅₀ of 0.88 卤 0.09 渭M, unveiling a novel biological activity for this well-studied natural product.