Abstract

Cancer diagnoses are on the rise and the development of anticancer treatments are becoming increasingly crucial. Leading research in the field of anticancer molecules has focused on antimitotic agents that target the colchicine- binding site of tubulin and halt cell proliferation. The colchicine-binding site has been shown to interact with Combretastatin A4, chalcones, and pyrrole-containing molecules that consist of a five-membered nitrogenous aromatic ring. This research focuses on the synthesis of pyrrole-containing molecules, their ability to inhibit the colchicine-binding site, and their potential to act as DNA cleaving agents. Chalcones will serve as the starting material with glycine ethyl ester as a key reagent to yield the pyrrole-containing molecules of interest. The primary objective of this project is to synthesize a library of chalcones and pyrrole-containing molecules to be examined for antimitotic and antitumor properties using an MTT assay. A dimethoxy chalcone (99% yield), a tetramethoxy hydroxyl chalcone (76% yield), a dimethoxy nitro chalcone (94% crude yield), and a methoxy amino chalcone (74% crude yield) have been synthesized to serve as starting material in the synthesis of various pyrroles. The dimethoxy chalcone, glycine ethyl ester, and N-bromosuccinimide were utilized in a Michael addition reaction, and in a subsequent bromination reaction, to synthesize a brominated pyrrole containing the A and B rings of the dimethoxy chalcone. The tetramethoxy hydroxyl chalcone, structurally resembling Combretastatin A4, was also utilized in a Michael addition reaction and subsequent bromination reaction in an attempt to synthesize the key pyrrole intermediate of interest. In future steps of this research project, this key pyrrole intermediate will undergo a coupling reaction to yield a dienyne substituted pyrrole that will be examined for its potential to act as a DNA cleaving agent.

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