Friday, February 12, 2016
James Olsen, La Salle College High School, Wyndmoor, PA
Due to the rising rate of resistance, new drugs to treat malaria have become important in recent years. The compound WR-965 was discovered by the Walter Reed Army Medical Center in the 1960s and was shown clinically to treat resistant malaria but was abandoned in favor of other pursuits. In this project, WR-965 was compared to Quinine, Chloroquine, and Mefloquine using molecular modeling techniques. Macromodel was used to generate low energy conformations of each antimalarial compound. The conformations of Quinine, Chloroquine, and Mefloquine were individually compared to those generated for WR-965 using Phase with select, pre-defined pharmacophore points. The results of these comparisons were then used to design six analogs of WR-965 for synthesis. In order to initiate synthetic protocols, a collaboration with an academic chemistry laboratory was achieved. Synthetic organic chemistry techniques were learned, an accessible synthetic scheme was designed, and five of the six steps of a synthetic route to a key synthetic target (Analog 3), including a challenging Suzuki cross-coupling reaction, were successfully completed. Synthesis of additional analogs was initiated and will be described. Upon completion, the analogs of WR-965 will be tested against various resistant and wild-type strains of malaria in collaboration with an academic biology laboratory.