Natural products targeted for potential drugs

Natural products provide a validated basis for protein-drug interactions that should be exploited as a tool for rational drug design, Griffith University's Prof Ron Quinn told delegates at the Australian Health and Medical Research Congress last week.

Speaking at the Drug Discovery Symposium at the Congress, Quinn explained how the Natural Products Discovery centre, a joint venture, formerly known as AstraZeneca R&D Griffith University, between pharmaceutical giant AstraZeneca and Griffith University (GU) since 1993, was screening a vast array of extracts from Australian plants, marine life and micro-organisms for potential therapeutic activity.

But in addition to being a rich source of new drug leads that are discovered in a hit-or miss fashion, Quinn believes that natural products are a mine of information about biochemical interactions.

"All natural products are made by enzymes and interact with other proteins," he explained. "The fundamental thing here is that natural products are validated in biological space. How can we capitalise on that?"

Quinn said that techniques like crystallography would provide insight into how natural products bind to their target proteins. Genomics could provide information on similar domains in other proteins from other organisms.

"If all natural products bind to proteins [in the original organism], it could be that they will also bind to similar human proteins," he explained.

Ultimately, he said, knowledge about the requirements for binding, such as the specific shape of the molecule and how it fit into the binding site, or functional groups attached to the molecule that interacted with specific amino acids in the binding site, could be harnessed for rational drug design.

"You could modify groups on a specific template or modify the template to fit a protein," Quinn suggested.

Quinn, who is the director of the Natural Products Discovery centre, plans to devote quite a bit of his research to the idea. Meanwhile, AstraZeneca has renewed its commitment to the joint venture by extending funding through 2007.

The centre is one of AstraZeneca's five sites for drug discovery around the world, and the only one utilising natural products. Utilising high throughput screens, as many as 100,000 extracts can be screened per day.

Quinn said that AstraZeneca supplies both generic and proprietary screens to the centre, and about 20 are performed every year, with a variety of targets. Once potential drug lead compounds are identified and chemically characterised, they go back to AstraZeneca for pre-clinical development.

"We've got compounds in the development pathway, but none yet in humans," Quinn said.

One potential advantage for GU is that rights to any compounds discovered by Natural Products Discovery that AstraZeneca decides not to pursue go back to the university. While it hasn't happened yet, it's always a possibility, said Quinn.

And royalties from products that make it through the pipeline onto the market will eventually flow on to the university.

"Big companies only go after blockbusters. There's a potential for a significant return from royalties for the university. You don't need much of several billion dollars!" Quinn said.