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Evaluating Anticancer Activity of Isomeric Analogues of the 3,4‐Diarylfuranone, PY‐407‐C

Microtubules are filamentous proteins that comprise the cytoskeleton of eukaryotic cells and play an essential role in cell structure, mitosis, migration, and signaling. The function of these proteins is dependent on their ability to exhibit dynamic instability, or the ability to spontaneously depolymerize and polymerize. Microtubule targeting agents are promising anti‐cancer therapeutics, that inhibit the dynamic instability of microtubules by destabilizing or stabilizing the proteins. Our lab previously showed that the 3,4‐diarylfuranone, PY‐407‐C, exhibits nanomolar toxicity on U937 cells. The National Cancer Institute has confirmed this activity on several other cell lines (NCI‐60 assay), and algorithms suggested that it binds tubulin, which we confirmed. The goal of this project is to assess the potency of isomeric analogues of PY‐407‐C on U937 cells using a cytotoxicity assay. Results suggest that particular substitution patterns lead to low micromolar and nanomolar effectiveness. The results of this next generation of compounds will provide a better understanding of how to maximize potency and guide the synthesis of future analogues.