A UT Arlington team researching ruthenium compounds as possible anti-cancer drugs has discovered a way to make their complexes more effective against cancer cells and less toxic to healthy cells in lab tests.

Professor Frederick MacDonnell, of the UT Arlington Department of Chemistry and Biochemistry, presented his work this month at the 24th International Symposium on Chiral Discrimination in Fort Worth. His presentation was called: "In vitro and in vivo responses to the chirality of ruthenium-based anti-cancer drugs."

Platinum-based drugs are currently the first line of treatment for many cancer patients. Scientists working with similar elements, such as ruthenium, hope to develop effective, less toxic alternative chemotherapy drugs.

The ruthenium-based complexes used in MacDonnell's study are chiral molecules - non-superimposable mirror images known as either "right-handed" or "left-handed" enantiomers depending upon their chemical structure. The researchers used five different chiral ruthenium complexes to try to shrink non-small cell lung cancer samples in the lab. They found that the right-handed configurations were twice as effective as the left-handed configurations. They also saw that the right-handed configurations were twice as well tolerated in terms of acute toxicity as the left-handed configurations.

"What we've found is that the right-handed configuration of this drug is working for you in two fashions, both of them beneficial," MacDonnell said. "It is both more effective at killing cancer cells and is less toxic to the organism -sort of a double-whammy."

MacDonnell's co-presenters at the conference were Abhishek Yadav, Thamara Jaranatne and Arthi Krishnan, all past graduate students at UT Arlington.

MacDonnell also noted that these ruthenium compounds work well against tumor cells under hypoxic, or low-oxygen, conditions. Such compounds could be useful to target the subpopulation of hypoxic

MacDonnell

cancer cells in solid tumors, as these cells are often the most resistant to drug treatment.

This research was funded through a $222,000 grant from the National Institutes of Health. The University of Texas System has applied for a U.S. patent on MacDonnell's discoveries.

"Relatively few pharmaceuticals are organo-metallic compounds, but those that are have powerful effects. Dr. MacDonnell has developed ruthenium-based compounds that have great potential as cancer drugs," said Daniel Armstrong, a UT Arlington professor and internationally known chemist who holds the Robert A. Welch Chair in Chemistry. Armstrong was a lead organizer of the International Symposium on Chiral Discrimination.

Posted June 18, 2012