INVESTIGATING THE POTENTIAL OF NOVEL BORON CONTAINING COMPOUNDS

Candidate: Mohammed Ayan Chhipa
Supervisor: Dr. Sarah Sabatinos

ABSTRACT

The use of boron in pharmaceutical drug design has been recent with Bortezomib (VelcadeTM) being the first compound approved for clinical use in 2003. Over the last 20 years, a handful of compounds have been approved as therapies for various cancers and microbial infections. However, the use of boron continues to lag behind other elements. Most compounds on the market have specific boron moieties that either include boronic acid, benzoxaborole, or cyclic boronate esters. To expand the boron toolkit, we screened 43 novel boron compounds to determine anti-proliferative effects against fungal, bacterial and cancer cells. These compounds include 3 novel boron moieties, including BF2, Bcat, and BPh2. We found that K-NO2-BPh2 strongly inhibits proliferation of S. pombe cells, with an IC50 value of 4 μM. Additionally, we found this compound to decrease ergosterol levels. These are steroids responsible for the integrity of fungal cell membranes. Several compounds showed selectivity to 3 pancreatic cancer lines (PANC1, BxPC3 and HPAC). At the same time, these compounds had limited impact on RPE proliferation. Morphologically speaking, PANC1 showed an abnormal phenotype such as cell protrusion and branching. Overall, we show the impact of our novel compounds in an attempt to expand the boron toolkit for drug development.