Studies in benzimidazo [2,1-a] isoquinoline chemistry
Studies in Benzimidazo[2,1-a]isoquinoline Chemistry by Michael John Donaghy B. Sc. (Hons.) Ellipticine, a member of the pyrido[4,3-b]carbazole alkaloid family first isolated in 1959 from the leaves of the plant Ochrosia Elliptica has been shown to possess anti-cancer activity against various tumours. Ellipticine is thought to undergo biological oxidation to give the more active 9-hydroxyellipticine that is subsequently converted to a highly reactive quinone-imine intermediate. The quinone-imine is then thought to interact with bionucleophiles in the body promoting cell death. The aim of the project was to synthesise a series of benzimidazo[2,1-a]isoquinolines. The benzimidazo[2,1-c]isoquinolines were similar in general structure to ellipticines and should therefore undergo similar biological reactions. The target benzimidazo[2,1-a]isoquinolines have been screened to evaluate their ability to inhibit the enzyme topoisomerase II that is involved in DNA replication and ultimately cell reproduction. The target compounds have also been evaluated by the American National Cancer Institute.