Synthesis of Novel VCP Inhibitors Through a Microwave-assisted Multicomponent Reaction with Acyclic Amidines

Speaker: Dr. Jacqueline Smith, Bowie State University

Host: NOBCChE

Abstract: Valosine-Containing Protein (VCP) is an ATPase shown to be upregulated in resistant breast cancer. A variety of heterocyclic small molecules have been shown to be inhibitors of VCP. However, mutations in the VCP binding site of the most efficient inhibitors have been observed. Using intelligent drug design, we predict that trisubstituted imidazoles will act as inhibitors of VCP. In order to access these imidazoles, we have expanded the Groebke-Blackburn-Bienayme’ Reaction (GBBR) to include acyclic amidines. Aromatic amidines have been shown to efficiently produce the trisubstituted ligands known as BITIs and DITIs. With these ligands in hand, biochemical and cellular assays will be used to assess the effectiveness of these compounds on VCP. Ultimately these compounds will be tested in resistance cancer mouse models. Future work will be conducted to determine the effects of substituents on aromatic amidines.

Biochemistry Seminar