Inhibition of Phosphatidylinositol-3-kinase by the Furanosteroid Hibiscone C
Besley, C.; Rhinehart, D. P.; Ammons, T.; Goess, B. C.; Rawlings, J. S. Inhibition of Phosphatidylinositol-3-kinase by the Furanosteroid Hibiscone C. Bioorg. Med. Chem. Lett., 2017, 27, 3087-3091.
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.
Bioorganic & Medicinal Chemistry Letters