Drug Discovery

Research from the lab of Prof. Robert Sheaff and Prof. Syed Hussaini

Enaminones are important building blocks in organic synthesis that are used in producing natural products and developing pharmaceuticals, peptidomimetics, ligands for catalysis, and chiral auxiliaries. Dr. Hussaini’s lab synthesized a library of novel enaminones with functional groups similar to those of amino acids, which raised the possibility some of the compounds might have biological activity. A preliminary screen identified several compounds that decreased cell viability, suggesting the existence of biological targets. Based on their similarity to amino acid functional groups, it was hypothesized they might target enzymes involved in protein metabolism. The library was therefore screened for the ability to inhibit proteases, which degrade proteins by interacting with specific amino acids in the polypeptide chain. The screen identified several compounds that inhibit specific proteases in the proteasome, an important therapeutic target that degrades critical cellular proteins. These molecules are being further evaluated as potential drug candidates.