The use of metals in drug molecules could offer major benefits, such as allowing for lower therapeutic dosages and fewer side effects. In particular, a special class of metal compounds called catalysts has often been overlooked in drug discovery research.
Loi Do, associate professor of chemistry at the University of Houston, is pursuing novel inorganic platforms for drug discovery using a $1.53 million grant from the National Institute of General Medical Sciences.
These small-molecule intracellular metal catalysts work differently than typical organic molecules, offering potentially powerful new ways to combat diseases. Do said both scientific barriers and concerns about toxicity have limited their use.
“The public, when you ask about metals, automatically think they’re toxic. That’s not true,” he said. “Our bodies require certain metal elements to function. Understanding the roles of metals in human health continues to be a very important and active research area.”
The use of metals in medicine is actually not new. For example, Cisplatin is a chemotherapy drug based on platinum that is commonly prescribed for the treatment of a variety of cancers. Despite the proven benefits of metals in drugs, Do said most pharmaceutical research still focus on organic molecules or proteins. His work has relevance for treating diseases related to oxidative stress, including heart disease, neurodegenerative disorders, and cancer.
For this project, Do will create synthetic forms of biological macromolecules that detoxify aldehydes, a class of substances typically found in low levels in healthy people. High aldehyde levels, however, indicate biochemical imbalance and could lead to disease development over time.
“If we can selectively neutralize those toxic aldehydes, we can minimize damage to the body due to oxidative stress,” he said.
Do’s lab does both synthetic chemistry – creating molecules for specific purposes – and chemical biology, allowing them to test their compounds to see if and how well they work. “We have control of the entire process,” he said. “When we make new metal complexes, we can test them ourselves in our cell culture lab. That’s going to help us improve the compound’s efficacy because we can identify where the problems are early in the drug discovery process. It makes the process more efficient.”
“Ideally, you would give a patient a single dose of this drug, and because of its unique mechanism, it would have a long-lasting effect,” he said. “With most current drugs, the drug molecule is consumed, so the patient has to keep taking more doses to maintain the therapeutic level of the drug. With a metal catalyst, you could achieve that effect over a longer period of time.”