2019-2020 Faculty Research Grants

Marlene Murray and Desmond Murray (Biology, Chemistry)

Design and Development of Novel Hybrid Pharmaceuticals for Bipolar Disorder

The purpose of this proposed collaborative, interdisciplinary (chemistry and molecular biology) research project is systematic design and development of novel hybrid small molecules for treatment of bipolar disorder. This proposal is specifically based on (a) Dr. Marlene Murray’s ongoing interest and molecular biology research in bipolar disorder and in monitoring inositol levels in response to potential anti-bipolar agents in yeast models, and (b) the development of synthetic methodology for creating biologically relevant hybrid acylals and acylureas in the laboratories of Dr. Desmond Murray. An over-50 year decline in psychiatric drug development in the pharmaceutical industry has created an urgent need for new and better psychotropic medications, in general, and for bipolar disorder, in particular, with the need to minimize the often unmanageable side effects of many current bipolar disorder drugs. With the discovery of biomolecular targets for psychiatric disorders, there are signs of increasing researcher interest in the field of psychiatric drug discovery and the growing research and advances in the field of small molecule hybrid drug medicinal chemistry. Our proposed project lies at the cutting edge and intersection of multiple needs and fields and provides us with an opportunity for pedagogical instruction and research opportunities for our high school, undergraduate and graduate students. Our synthetic strategy to obtain the proposed hybrid ‘psychotropic’ molecules involves simple, multistep one-flask procedures based on our advances in electrophilic carbonyl addition (ECA) chemistry. This facilitates rapid access to a wide diversity of molecules to investigate structure–bioactivity relationships. A fluorometric inositol bioassay protocol will be used to measure inositol concentrations of cells grown in the absence and presence of our hybrid bifunctional compounds.