Antioxidants are molecules that can counteract the damaging effects of oxygen in tissues and other materials. They have long been studied for their potential effects in fighting cancer and other serious disease such as heart disease.
While research into vitamin E is so far inconclusive, the wealth of positive reports has created a booming market for the antioxidant vitamin in foods and cosmetics. Much of this is prompted by consumer demand to slow ageing and the diseases related to it. The market for antioxidants in North America is estimated at more than $800 million per year.
The new antioxidants were tested in vitro on cholesterol molecules, the scientists found they protected the LDL molecules from oxidation. This means that they could become extremely useful in the fight against the onset of coronary artery disease.
"Vitamin E is nature's antioxidant and people have been trying to improve upon it for more than 20 years with only marginal success. We have taken a very big step in the right direction," said Ned A. Porter, the Stevenson Chair of Chemistry at Vanderbilt, supervisor of the developments made by graduate student Derek Pratt.
Reporting in a recent issue of Angewandte Chemie International Edition, the team describes the changes made to a-tocopherol, which is a phenol containing a ring made of six carbon atoms with a hydroxyl group (OH) attached.
Other scientists had tried to make better antioxidants by attaching a nitrogen atom to the carbon ring. Theoretically, these molecules should be stronger antioxidants but they proved to be impractical because they were unstable in air.
In addition to attaching a nitrogen atom to the ring, Pratt substituted a nitrogen atom for one of the carbon atoms in the ring itself. With both substitutions he predicted that the resulting molecules, called pyridinols, should be more stable in air.
Initial tests demonstrated that the resulting molecules did indeed act as effective antioxidants. It took a year to work out a 12-step process that produced the most effective member of this new class of compounds in quantities large enough for testing.
The Vanderbilt chemists sent samples to Professor G. F. Pedulli's lab at the University of Bologna in Italy, to test for antioxidant effectiveness. The best pyridinols the Vanderbilt chemists had created were found to be as much as 100 times more effective than vitamin E, say the scientists.
By attaching a chemical group that makes pyridinols 'greasy' - gives them a chemical affinity for fatty acids - the chemists then combined their antioxidants with low density lipoprotein and found that they appear to protect LDL molecules from oxidation. That may be significant because one popular theory for the cause of coronary artery disease is lipid oxidation.
"When we try to force lipid oxidation, we find that the pyridinols are much more effective inhibitors than vitamin E," said Porter.
The chemists are currently working to make pyridinols that look as much like vitamin E as possible. Another project aims to make pyridinols that are water soluble, unlike vitamin E. Water soluble varieties should perform a role similar to that of vitamin C: trapping and destroying water-soluble free radicals.
Researchers at the Vanderbilt University Medical Center, which has a patent pending on the compounds, will test these new compounds in animals.