PROBING THE MOLECULAR FUNCTION OF NOVEL BORON-CONTAINING COMPOUNDS

Candidate: Gillian Okura
Supervisor: Dr. Sarah Sabatinos

ABSTRACT

Boron-based therapeutics represent a new class of molecules that could possess various biomedical applications with antiviral, anticancer, antibacterial and antifungal activities. Relatively few boron-containing compounds (BCC) have been approved for clinical or commercial applications. Very little is known about the potential applications of most boron containing compounds against a wide range of diseases. This project focuses on the antiviral and anticancer arms of a larger screening project to determine biological activity of novel BCCs. First, using a human coronavirus model, we demonstrated the ability of our compounds to impair viral replication in both alpha- and beta- coronavirus models. Second, cell-based assays in human pancreatic and breast cancer cell lines demonstrated that novel BCCs show selective growth inhibition. The molecular functions of our compounds were probed in various cell lines using western blotting and cell cycle distribution analyses. These have revealed that our most effective BCCs in vitro likely impact different mechanism(s) in cancer cell killing than the commonly studied drug, bortezomib (VelcadeTM). Our results reaffirm the potential of boron chemistry and use of novel BCC in biomedical applications.