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Graduate Defense: Madison Dirks

August 11 @ 9:00 am - 10:00 am MDT

Thesis Information

Title: Bioactivity Assessment of Veratrum californicum Alkaloids

Program: Master of Science in Chemistry

Advisor: Dr. Owen McDougal, Chemistry and Biochemistry

Committee Members: Dr. Lisa Warner, Chemistry and Biochemistry, and Dr. Joseph Dumais, Chemistry and Biochemistry

Abstract

The native Idaho plant Veratrum californicum is known to contain steroidal alkaloids that function as inhibitors of hedgehog signaling, a pathway utilized for the growth and differentiation of more than 20 types of cancer. There are at least thirteen compounds that are completely uncharacterized, five with proposed identities, and the six known alkaloids veratrosine, cycloposine, veratramine, cyclopamine, isorubijervine, and muldamine all within Veratrum californicum. These molecules were extracted together and then separated into five fractions using high performance liquid chromatography. A mass spectrometry analysis was performed, proposing molecular formulas for each known and unknown alkaloid. The bioactivity of the raw extract and each fraction was assessed by comparison to a known concentration of cyclopamine, and it was found that three fractions had better hedgehog signaling suppression than cyclopamine. Fraction 1 was most potent, containing veratrosine, cycloposine, and an isomer of each, followed by Fractions 2 and 4, where Fraction 2 was proposed to be comprised of cycloposine, its isomer, veratrosine’s isomer, tetrahydrojervine, veratramine, and five unknown compounds, and Fraction 4 was composed of cyclopamine, likely muldamine, and six unknowns.