Medicinal chemistry
Synthetic organic chemistry
Natural products synthesis
We use synthetic organic chemistry and medicinal chemistry principles to create small molecules that advance the discovery of medicines for Neglected Tropical Diseases and bacterial infections that desperately need safer and/or more effective treatments. Our molecules are inspired by natural products, library screening, and known drugs. For example, the drug raloxifene, a selective estrogen receptor modulator, was shown to exhibit anti-Leishmania activity. Fortunately, through structural modifications, the estrogen receptor activity can be removed, while maintaining anti-Leismania activity. We studying the requirments for anti-Leishmania activity by strategically modifying the structure. Simultaneously, we probe for structural changes that improve the drug-like physiochemical properties, such as solubility and lipophilicity. Starting from a known drug has several advantages that dramatically accelerate the discovery of new therapeutics: a) structurally related compounds has already been prepared for previous drug discovery efforts; Eli Lilly and Company donated a library of structurally related analogs to our collaborator for evaluation, which provided a wealth of information about the structural requirements for activity; and b) the chemical scaffold has acceptable drug-like properties and data is available on multiple analogs. We use a variety of medicinal chemistry approaches, such as fragment based drug discovery, protein-crystal structure guided drug design, physiochemical property correlations, and computational approaches.