Scientists in Canada have successfully synthesized a natural compound that shows highly unusual potential to selectively treat melanoma, a type of skin cancer that is often fatal, and perhaps other cancers as well.
The study is the work of Professor Dennis G Hall of the Department of Chemistry, University of Alberta, Edmonton, and colleagues, and was published recently in the Journal of the American Chemical Society.
Over the last 30 years or so, explorers and scientists have discovered that our oceans are home to some very unusual bioactive compounds that show surprisingly strong cytotoxic, antibiotic, pesticidal and antifungal properties.
One such group, called the palmerolides, has been discovered in the seas of the Antartic, which until recently, because of extreme climate and isolation, have remained largely unexplored.
The palmerolides are a family of cytotoxic marine macrolides isolated from the rare Antarctic tunicate Synoicum adareanum (a type of sea squirt), which can only be found in the shallow waters around the Anvers Island on the Antarctic Peninsula.
One member of the palmerolides, Palmerolide A appears to have significantly increased selectivity for melanoma cancer cell lines.
However, there is a problem: how to get enough of it for researching and developing possible drugs. We can’t just wade into the Antartic sea and remove all the rare sea squirts; quite apart from the fact there aren’t enough of them, the place is tightly protected from commercial exploitation by the Antartic Treaty.
Thus the only option is to try and synthesize Palmerolide A, and that is where this study comes in.
Hall said it took three years for he and his team to successfully produce a synthetic form of Palmerolide A. He told the media that:
“The potency of palmerolide is exceptional and melanoma is a very aggressive cancer for which there is almost no chemotherapeutic recourse.”
“Natural substances like palmerolide offer real hope for such treatments,” he added, explaining that current chemotherapies for melanoma are not very effective:
“Less than a quarter of patients respond to chemotherapy and it typically only works for less than a year, and it has little to no effect on survival time,” said Hall.
He said that using Palmerolide A to target melanoma may prove to be more effective and less toxic to patients.
“One of the problems with most cancer drugs is the lack of selectivity for cancer cells versus normal cells. Preliminary data for Palmerolide A looks very promising in terms of solving this issue,” he added.
However, there are still many steps to complete before a drug based on Palmerolide A is commercially available. One of these is to change the structure of the compound to make it more “drug-like”, in other words smaller and more water-soluble, while not losing its potency.
Hall was full of optimism that he and his team at the University of Alberta were strong contenders in the race to develop a treatment for melanoma.
Drug companies have also expressed interest in taking palmerolides to the drug testing stage, and in 2007, the University of St Andrews in Scotland won a grant from the UK’s Engineering and Physical Sciences Research Council to develop ways of synthesizing palmerolides.
The palmerolides are so named because they were discovered in the waters surrounding Palmer Station, where marine scientists from the University of Alabama at Birmingham (UAB) are based. They sent samples to the US National Cancer Institute, where they discovered the potent anti-cancer activity of palmerolides.
“Catalytic Asymmetric Synthesis of Palmerolide A via Organoboron Methodology.”
Marlin Penner, Vivek Rauniyar, Ludwig T. Kaspar and Dennis G. Hall.
J. Am. Chem. Soc., 2009, 131 (40), pp 14216-14217.
DOI: 10.1021/ja906429c
Sources: University of Alberta, UAB in Antartica, Engineering and Physical Sciences Research Council.
Written by: Catharine Paddock, PhD