Duke University announced on Wednesday that its chemists have patented an efficient technique for synthesizing a marine algae extract in sufficient quantities to now test its ability to inhibit the growth of cancerous cells.
The researchers also deduced that this molecule, called largazole, acts on cells through the same chemical mechanism as other anti-cancer compounds on the market or in clinical trials.
Largazole was first extracted and identified from a blue-green algae collected in Florida. Guided by evidence of therapeutic benefits from extracts of a related algae, researchers demonstrated that largazole could impede breast cancer cell growth better than the anti-tumor drug Taxol without causing side effects on normal breast tissue.
But before the synthesizing tech, researchers in Florida isolated just one milligram, a very tiny amount, from natural sources that were very difficult to grow.
"We needed to develop a concise and efficient synthetic route to make enough largazole for animal studies," said Duke researchers.
They devised a method to produce gram-sized quantities -- about1,000 times more -- by identifying three key building blocks in largazole's ring-shaped molecular architecture. They were then able to use commercially available chemicals to make largazole in eight steps, netting a "very, very efficient" 20 percent yield.
The next task for Duke team was finding the origin of lagarzole's biological activity. The molecule appeared to initiate some signaling cascades that could affect inappropriately proliferating cells but not normal ones.
In the process of sleuthing this question, Duke researchers discovered that largazole was structurally similar to another molecule called FK228. FK228 is known to inhibit histone deacytelases (HDACs), enzymes regulating genetic activity that can foment cancerous cell growth.
The Duke team confirmed that, like FK228, largazole also suppressed HDACs. Another HDAC suppressor, marketed as Zolinza, has now been approved for the treatment of T-cell lymphoma. Others, including FK228, are undergoing clinical trials as anti-cancer drugs.
Duke researchers are now doing follow-up research aimed at changing largazole's structure to increase its effects on cell growth. It could be a very good drug candidate for the treatment of various cancers.
(Xinhua News Agency August 22,2008)