Toxin, take two
Medicinal chemists modify sea bacteria byproduct for use as potential cancer drug
By John Pastor
UF researchers have modified a toxic chemical produced by tiny marine microbes and successfully deployed it against laboratory models of colon cancer.
Writing in ACS Medicinal Chemistry Letters, UF medicinal chemists described how they took a generally lethal byproduct of marine cyanobacteria and made it more specifically toxic — to cancer cells.
When the scientists gave low doses of the compound to mice with a form of colon cancer, they found that it inhibited tumor growth without the overall poisonous effect of the natural product. Even at relatively high doses, the agent was effective and safe.
“Sometimes nature needs a helping human hand to further optimize these products of evolution to treat human diseases,” said Hendrik Luesch, Ph.D., an associate professor of medicinal chemistry in the College of Pharmacy. “Based on what we learned about apratoxins’ mechanism of action, we knew this compound class had great potential for use in anticancer therapies; however, the natural product itself is too toxic to become a therapeutic.”
The researchers synthesized several apratoxin compounds that were similar to the original except for slight differences in composition, designing one that proved to be extremely potent against the cancer cells in cultures and in mice, but without the overwhelming toxicity.
Apratoxin is produced by cyanobacteria, microbes that have evolved toxins to fend off predators and cope with harsh conditions in a marine environment. Collectively known as blue-green algae — a misnomer because the single-celled organisms are not algae or members of the plant kingdom — a wide variety of cyanobacteria species exists in both sea and freshwater environments.