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Tuesday, December 6 • 3:20pm - 4:00pm
Combretastatin A-4 Analog Bearing Indole Chalcone Moiety

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Drugs that target tubulin polymerization have largely been focused on in the field of cancer research. Combretastatin A-4 (CA-4) binds to the colchicine site of ß-tubulin, and therefore inhibits tubulin polymerization. Inhibiting this function leads to cell aptosis in tumoral vasculature, thus producing anti-cancer effects. Structural modifications of CA-4 have been made in various studies to increase the solubility of the compound, as well as binding affinity to the colchicine site. Studies in the literature have shown that incorporating indole and chalcone moiety in analogs of CA-4 has increased the efficacy of the drug. This research focuses on synthesizing an analog of CA-4 in which the trimethoxy A-ring of CA-4 is replaced with an indole ring, and possesses a chalcone core that connects the two heterocyclic rings. Synthesis of the substituted indole utilizes Hemetsberger-Knittel methodology, in which thermolysis of the vinyl azide allows the indole ring to form. The chalcone of interest is formed in the final step from the indole aldehyde and halogenated acetophenone. The brominated acetophenone was synthesized several times in order to acquire enough product so that it could be purified through column chromatography. Various reactions with a previous student's indole aldehyde were attempted, but the trials proved to be unsuccessful. Therefore, the indole synthesis was started from step 1 in order to obtain the desired indole product. So far, a protecting group has been added to a substituted benzaldehyde, which is required for the rest of the synthetic scheme. The indole synthesis needs to be completed so that the desired indole can be reacted with the brominated acetophenone, thus forming the target CA-4 analog.


Tuesday December 6, 2016 3:20pm - 4:00pm PST
014 Zeis Hall