Flavonols in food, key to healthy eating?

University of Melbourne scientists may have found the secret of the fresh fruit and vegetables centred ‘Mediterranean diet’.

Their research, based in the University’s Bio21 Molecular Science and Biotechnology Institute, points to key biochemical ingredients in fresh fruit and vegetables (and red wine) known as flavonols.

They have found flavonols relax the tissue in blood vessel walls, improving blood flow, and can also protect against the reactive oxygen and nitrogen compounds which cause tissue damage during and after heart attacks.

The research, led by Associate Professor Owen Woodman (Pharmacology), suggests flavonols are good candidates for the development of drugs to prevent and treat heart disease.

Because flavonols are naturally occurring compounds we ingest every day, they are unlikely to have side effects. But there is one snag. They do not dissolve in water, which makes them difficult to administer.

Working with Associate Professor Woodman’s team to develop water-soluble flavonols with improved biological activity is organic chemist, Dr Spencer Williams (Chemistry/Bio21 Institute).

Dr Williams is a specialist in developing ways of making compounds, such as flavonols, in the laboratory. He examines the structure of molecules, invents new ones to answer specific biological questions, and gets someone to make them.

A way to synthesise the key molecule in flavonols has been developed and Dr Williams has identified where to add chemical groups to the structure to make the compound more water soluble and not detract from its biological activity. His expertise in building molecules is playing a role also in research led by Associate Professor Malcolm McConville (Biochemistry) at the Bio21 Institute.

Dr Williams is investigating how the parasites that cause two major human diseases, leishmaniasis and tuberculosis, make and use carbohydrates. Part of the idea of this work is to provide new ways of protecting people against these diseases by disrupting the parasites that cause them.

“For both of these diseases there has been a lack of input by pharmaceutical companies, because they tend to affect the developing world, and the money isn’t there,” he says.

“It’s important that public agencies fast track research in these areas, so perhaps pharmaceutical companies will become interested in later stage research and development.”

Leishmania parasites are protozoans which are spread by a mosquito-like sandfly. They affect about 12 million people a year causing two main forms of disease – cutaneous (sores on the skin), and visceral (enlarged spleens and livers).

Instead of storing glucose as carbohydrates like starch or glycogen, as higher plants and animals do, leishmanias store another sugar, mannose, in a form known as mannan. The researchers believe mannan is essential to the parasite’s ability to survive in the human body and are studying how it is formed.

Mannose is also an important component in the structure of the cell wall of the tuberculosis bacterium. TB is the world’s major cause of bacterial death, the leading killer of women of childbearing age, and the eventual cause of one in three deaths from HIV. The bacterium’s cell wall forms a barrier to drugs, making it difficult to treat.

Associate Professor McConville, Dr Williams, and others are investigating how the wall is built and are seeking ways of disrupting the process.

Already they have discovered that the enzymes involved in mannan biosynthesis are novel and thus are promising drug targets.