Inhibition of mitogen-activated protein kinase p38α by rooperol and analogues
Davis, Chelsea S.
Cancer therapeutic drugs have evolved over time in correlation with the understanding of the biological mechanisms which they affect. Many anti-cancer leads have been found in natural sources. The African potato, Hypoxis hemerocallidea, is widely used in South African as a medicinal plant for the treatment of cancer and other diseases. Extracts from the corms of this plant contain the major biologically active component hypoxoside. Hypoxoside is hydrolyzed to the anti-cancer agent rooperol ((1,5-bis(3’,4’-dihydroxyphenyl) pent-1-en-4-yne) which has been shown to inhibit cancer cell lines. In a Phase I clinical trial, lung cancer patients showed promising anticancer activity results, with one patient cancer free after 5 years. Rooperol is metabolized into biologically inactive forms with glucuronic acid and sulfates groups. Analogues of rooperol have been synthesized with the goal of increasing metabolic stability while preserving anti-cancer activity. Rooperol has been seen to inhibit microtubule formation as well as inhibit mitogen-activated protein kinase p38α which is known to influence control of the cell cycle, inflammation, and cancer. The goal of this research was to investigate the ability of rooperol and analogues to inhibit p38α. The study used in vitro ELISA and luminescent ADP assay to quantify kinase activity. Then in silico docking studies were done to compare analogues and rooperol in binding to p38α. With this docking information in correlation with cytotoxicity to identify possible anti-cancer or anti-inflammatory compounds.
Natural products, Kinase inhibitors, Rooperol, p38α
Davis, C. S. (2020). <i>Inhibition of mitogen-activated protein kinase p38α by rooperol and analogues</i> (Unpublished thesis). Texas State University, San Marcos, Texas.