Studies on antimalarial activity, physicochemical properties and mechanism of action of 4(1H)-quinolones and artemisinin

• Online Access: http://hdl.handle.net/2047/D20211686

Malaria continues to be a global health problem, affecting hundreds of millions and killing hundreds of thousands every year. In order to heed the call for new treatments for malaria, the Manetsch lab has turned to the studies of previously abandoned antimalarials as well as mechanism of action studies in order to improve these compounds. ICI 56,780 is one of these historic compounds. Originally synthesized in 1967, it was found to have blood schizonticidal activity as well as causal prophylactic action. Though it was also found to be curative in rhesus monkeys, poor bioavailability and a penchant for resistance led to the abandonment of ICI 56,780. In addition to historical compounds, we have completed research on a current treatment for malaria. Artemisinin was isolated in 1972 from Artemisia annua, which had been used in Chinese herbal medicine for over 2000 years. Artemisinin-based combination therapies (ACTs) are the current leading treatment for uncomplicated malaria, but recently, resistance to ACTs has been documented at the Thai-Cambodian border.