Designer molecules that combine metals such as copper with natural organic materials could one day attack viruses in the body and treat a wide range of diseases.
That's the finding of chemists at Ohio State University, who have successfully tested such molecules against portions of HIV and Hepatitis C virus RNA in the laboratory. They've also created molecules that act like ACE, or angiotensin-converting enzyme, inhibitors - drugs that are used to lower blood pressure.
At the American Chemical Society national meeting in Washington, DC, project leader James Cowan described how the same patent-pending technology could one day produce novel anti-tumor agents.
Drugs based on these molecules could produce fewer side effects compared to some of today's treatments, and they could also combat drug resistance, said Cowan, professor of chemistry at Ohio State.
Pharmaceutical companies tend to make drugs from the same limited set of ingredients, drawing upon only about a half-dozen of the more than 100 known chemical elements, Cowan explained. At the same time, drug-resistant bacteria and viruses are emerging.
"Faced with a problem like that, you can't ignore 95 percent of the periodic table," he said. "We have to start broadening the landscape of drug design."
His new molecules, called metal coordination complexes, mimic the activity of natural enzymes that break apart DNA, RNA, and proteins in the body.
Cowan and his colleagues have tailor-made different complexes to break apart portions of RNA that enable HIV and Hepatitis C viruses to function, as well as the ACE enzyme that constricts blood vessels in the body. In test tubes and in cell cultures of E. coli, the complexes targeted these particular RNA structures and enzymes and destroyed them.
The complexes work in one of two ways. Some use a process called redox chemistry to steal electrons from the bonds holding the target molecule together. Others use hydrolysis, meaning that they break down the target's chemical waterproofing, so that the water that is naturally present in a cell dissolves the target.
That's what makes these complexes different from most drugs.
"Most drugs are designed to inhibit - that is, they will bind to a protein molecule and just block its function," Cowan said. "But with metals you have the option of completely destroying the target."
He hopes that with proper tailoring to certain metabolic enzymes, these strategies could work against cancer. He also sees applications in homeland security, such as complexes that destroy the anthrax bacterium.
Even though these new complexes are partly made of metal, drugs based on them could potentially be less toxic to the body than conventional treatments.
Metals can be toxic, but so can some organic molecules that are used as drugs, Cowan pointed out.