We know that, carborane is a cluster composed of boron and carbon atoms. Like many of the related boranes, these clusters are polyhedra and are similarly classified as closo-, nido-, arachno-, hypho-, etc. based on whether they represent a complete (closo-) polyhedron, or a polyhedron that is missing one (nido-), two (arachno-), or more vertices. Interesting examples of carboranes are the extremely stable icosahedral closo-carboranes.
A prominent example is the charge-neutral C2B10H12 or o-carborane with the prefix o derived from ortho, which has been explored for use in a wide range of applications from heat-resistant polymers to medical applications.
Now researchers lead by Dr. Lee of University of Missouri used carboranes to build new drugs designed to shut off a cancer cell's energy production, which is vital for the cell's survival. All cells produce energy through complex, multi-step processes. The key to an effective drug is targeting the process that cancer cells depend on more than healthy cells. By increasing the binding strength of a drug, a smaller dose is required, minimizing side effects and increasing the effectiveness of the therapy. With carboranes, Lee found that the drug is able to bind 10 times more powerfully.
"The reason why these drugs bind stronger to their target is because carboranes exploit a unique and very strong form of hydrogen bonding, the strongest form of interactions for drugs," Lee said.
Lee said that this discovery also will lead to further uses for the drug.
"Too often, after radiation or chemotherapy, cancer cells repair themselves and reinvade the body," Lee said. "This drug not only selectively shuts off the energy production for the cancer cells, but it also inhibits the processes that allow those cancer cells to repair themselves. When we tested our carborane-based drugs, we found that they were unimaginably potent. So far, we have tested this on breast, lung and colon cancer, all with exceptional results."
According to Lee, this is the first study to show systematically how carboranes can improve the activity of a drug. Lee believes this discovery will open additional possibilities of improving drugs that are used to treat other diseases, not just cancer.
"The end result is that these new drugs could be many thousands of times more potent than the drugs that are used in the clinics today," Lee said.Carboranes Increase the Potency of Small Molecule Inhibitors of Nicotinamide Phosphoribosyltranferase - Journal of Medicinal Chemistry (ACS Publications)
