On October 3, 2024, after 2+ years of research, Edward Njoo, Ph.D. (Stanford University) ASDRP's Director of Research and Chair of the Department of Chemistry and Biochemistry, and his team of high school student researchers published in Natural Product Research! Congratulations to the entire team - a job very very well done. The Njoo Research Group in the Department of Chemistry at ASDRP works on research projects that cover Synthesis, Physical Organic Chemistry, Catalysis, Chemical Biology, Spectroscopy, Medicinal Chemistry.
"C-4 analogues of podophyllotoxin as tubulin inhibitors: synthesis, biological evaluation, and structure-activity relationship." Natural Product Research 2024, 1-7. ONLINE! DOI: https://doi.org/10.1080/14786419.2024.2410410
Abstract by the Njoo Research Group
The diversity of lignan small molecules derived from podophyllotoxin, a non-covalent tubulin inhibitor isolated from the Podophyllum family, has led to the clinical development of FDA-approved anticancer agents etoposide and teniposide. While these two compounds share the same tetracyclic core as podophyllotoxin, two subtle structural changes—4’ demethylation on the aromatic ring and stereospecific glycosylation at the C-4 hydroxyl—result in an alternate biological mechanism. Given the immense pharmacological importance of altering the C-4 position, we synthesised and evaluated a systematic library of diversified esters to establish a structure-activity relationship regarding modification at C-4 on the properties of podophyllotoxin. We determined the biological activity of these esters through cell viability assays, computer docking models, tubulin polymerisation assays, and cell cycle analysis. Altogether, we demonstrate that increasing steric hindrance at C-4 leads to a loss in potency against human cancer cells but has a significantly lesser impact on cell-free tubulin inhibition.
Authors: Breanna Lu, Northwestern University & Leland High School '24; Lexi Xu, Rice University & Leland High School '24; Harriet Chen, University of California, Los Angeles & Las Lomas High School '24; Grace Yu, American High School '25; Kimberly Khow, University of California, San Diego & Amador Valley High School '24; Stella Yang, The Harker School '26; Arushi Dinker, Rice University & Mission San Jose High School '24; Edward Njoo, Ph.D., ASDRP Director of Research.
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