Synthesis of a Novel Benzosuberene Analogue as an Anti-Cancer Agent
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Cancer is a highly prevalent disease characterized by abnormal growth and uncontrolled division of cells. While many current treatments modalities are powerful in their ability to damage and potentially destroy tumors, most therapeutic strategies lack selectivity towards cancer cells and unfortunately also damage normal healthy tissue. The search for anti-cancer agents that possess enhanced cytotoxicity and high selectivity has led to the discovery of benzosuberene-based analogues, of which certain analogues are potent vascular disrupting agents (VDAs) that destroy tumor vasculature and thus deprive the tumor of necessary nutrients and oxygen. The purpose of the project is to synthesize a novel benzosuberene analogue that is based on a lead compound (referred to as KGP18) discovered by the Pinney Research Group (Baylor University) and incorporates designed structural modifications. The ultimate goal is to obtain a new small-molecule, benzosuberene-based anti-cancer agent that demonstrates improved biological activity as both a cytotoxic (antiproliferative) agent and a functional VDA. While the project is ongoing, the chemical reactions that have been performed to date were successful. The current synthetic pathway suffers from low yield, thus one future direction involves modification of the synthesis in order to obtain greater efficiency. Upon completion of the synthesis, the novel benzosuberene compound will be subjected to biological evaluation (in collaboration with the Trawick Research Group, Baylor University) to analyze its cytotoxicity as an antiproliferative agent and selectivity as a potential VDA.