Inhibition of phosphatidylinositol-3-kinase by the furanosesquiterpenoid hibiscone C

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:27

Article

Besley, Caroline¹  Rhinehart, Dena P.²  Ammons, Taylor¹  Goess, Brian C.²  Rawlings, Jason S.¹ 

[1] Furman Univ, Dept Biol, 3300 Poinsett Highway, Greenville, SC 29613 USA

[2] Furman Univ, Dept Chem, 3300 Poinsett Highway, Greenville, SC 29613 USA

关键词: Hibiscone C;    Wortmannin;    PI3K;    Furanosteroid;    Furanosesquiterpenoid;   

DOI  :  10.1016/j.bmcl.2017.05.041

来源: Elsevier

【 摘 要 】

The phosphatidylinositol-3-kinase (PI3K) pathway regulates cellular metabolism and is upregulated in many cancers, making it an attractive chemotherapeutic target. Wortmannin is a potent inhibitor of PI3K; however, its potential as a chemotherapeutic is limited due to its instability, lack of selectivity, and lengthy chemical synthesis. In contrast, hibiscone C, a structurally simpler and less studied member of the furanosteroid family, has been expediently prepared by total synthesis. We demonstrate that hibiscone C competitively inhibits PI3K activity in intact cells, slows proliferation, and induces cell death. Hibiscone C may therefore serve as a productive scaffold for the development of therapeutically relevant PI3K inhibitors. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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