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UF medicinal chemists modify sea bacteria byproduct for use as potential cancer drug
Date:8/31/2011

University of Florida researchers have modified a toxic chemical produced by tiny marine microbes and successfully deployed it against laboratory models of colon cancer.

Writing today in ACS Medicinal Chemistry Letters, UF medicinal chemists describe 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 at UF's 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.

The compound acts as a single agent to reduce levels of two types of proteins that are targeted by cancer research labs around the world growth factors, and enzymes called tyrosine kinases, which act as receptors for the growth factors.

Known as apratoxin S4, the compound strips colon cancer cells of their ability to both secrete and use naturally occurring factors that fuel growth something that Luesch, postdoctoral chemist Oi-Yen Chen, Ph.D., and assistant scientist Yanxia Liu, Ph.D., say is a powerful "one-two punch" against mushrooming populations of cancer cells.

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Contact: John Pastor
jdpastor@ufl.edu
352-273-5815
University of Florida
Source:Eurekalert

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