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Medicinal chemistry research in my lab is a collaborative exercise where we engage other scientists with complimentary interests. Currently, we are engaged in discovery of protein kinase inhibitors for anti infective and anti inflammatory applications, and the discovery of new agents useful for treatment of memory disorders. We are working with others at MSU as well as scientists in other universities and research institutes.
PDE11A4 is an enzyme expressed in a region of the brain that plays an important role in memory. This enzyme regulates signal transduction in these cells and is increasingly expressed as mammals age. Our collaborator at the University of Maryland showed that knockout mice suffer from less age related memory decline compared to their wild type litter mates. We aim to identify a selective, orally active PDE11A4 inhibitor to test the hypothesis that a drug like small molecule will work in a similar manner. My laboratory synthesizes these new molecules and we work with researchers at Boston College, the University of Maryland, Temple University and Vanderbilt University to profile these candidates. Our research is funded by the US National Institutes of Health.
Protein kinase inhibitors for parasitic diseases
Collaborative drug discovery research is being carried out with Professor John Siekierka and coworkers in his laboratory and with researchers at Rutgers. Colleagues in my lab are synthesizing new analogs of a lead structure as potential protein kinase inhibitors. These compounds are being evaluated in Professor Siekierka's lab for activity against the target kinase and against the parasite for activity. Scientists at Rutgers carry out more detailed studies with selected new molecules to evaluate their effectiveness in cellular models of malaria. Together the team hopes to be able to identify molecules suitable for testing in humans to treat parasitic diseases.
Synthesis of unusual conformationally restricted diamines
We are synthesizing new molecules that contain two different amino groups (diamines) whose shape (conformation) is restricted due to the nature of the structure. These molecules can be used to explore structure-activity relationships at receptors and enzymes of biological interest. By exploring and defining the shape, distance and relative geometry of the diamine, we can discover useful biologically active molecules.