Legend
has it that Ralph Waldo Emerson once said, “Build a better mousetrap,
and the world will beat a path to your door.” University of Missouri
researchers are doing just that, but instead of building mousetraps, the
scientists are targeting cancer drugs. In a new study, MU medicinal
chemists have taken an existing drug that is being developed for use in
fighting certain types of cancer, added a special structure to it, and
created a more potent, efficient weapon against cancer.

   

“Over
the past decade, we have seen an increasing interest in using
carboranes in drug design,” said Mark W. Lee Jr., assistant professor of
chemistry in College of Arts and Science. “Carboranes are clusters of
three elements—boron, carbon and hydrogen. Carboranes don’t fight cancer
directly, but they aid in the ability of a drug to bind more tightly to
its target, creating a more potent mechanism for destroying the cancer
cells.”

In
the study, Lee and his research team 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.

   

While
it will be several years before the new drug would be available on the
market, Lee said that clinical trials could begin within the next two
years. Additionally, further testing on other types of cancer is
underway. The study was published in the Journal of Medicinal Chemistry, a publication of the American Chemical Society.

Source: University of Missouri