Scientists in London are turning to sea sponges to help them learn more about anti-cancer drugs.
Using his £106,079 grant from the Association for International Cancer Research (AICR) Dr Matthew Fuchter and his team are investigating a naturally-occurring chemical found in the sea sponge.
Molecules found in deep sea organisms are used in research into a number of diseases, including malaria and cancer. The particular sea sponge under investigation naturally contains the chemical psammaplin A which is reported to be a powerful blocker of several components of the processing machinery in cancer cells, preventing them from growing and dividing. Dr Fuchter and his team from Imperial College London have discovered a new way of making psammaplin A which has the potential to inspire novel anti-cancer drugs.
This new route allows the researchers to make variations of the psammaplin A chemical and to use those varients to understand the anti-cancer activity of this natural product. Knowledge gained from this endeavour will assist subsequent drug design efforts. Dr Fuchter's preliminary results show that these psammaplin A variants are more potent than nature's own attempts and could form the basis of new, selective drugs, in the future.
Said Dr Fuchter: "New chemical routes towards the natural product psammaplin A were developed with the particular view to preparing diverse variants for biological assessment. These routes utilize cheap and commercially available starting materials, and allowed access to psammaplin A variants not accessible via currently reported methods.
"Preliminary biological studies revealed these compounds which block the enzyme histone deacetylase 1 (HDAC1, class I), are the most potent non-peptidic inhibitors of the enzyme histone deacetylase 1 (HDAC1, class I) discovered so far. Interestingly, psammaplin A and our man-made variants show high selectivity in lab-based experiments, an important feature for the design and manufacture of future drugs."
The international charity's youngest grant holder, Dr Fuchter (31) said his AICR funding had been a "milestone" in his career and without it his work to design new drugs with the potential to enable people to survive cancer would not have been possible.
"I was advised AICR was a good organisation to approach for funding cancer research," he explained. "I was also advised that they were supportive of early career academics. When I got the approval for the grant I was ecstatic. It was a real milestone for a young academic like me. AICR's support is fantastic. It has really enabled me to start my independent research and build up expertise in cancer research."
Dr Mark Matfield, AICR's scientific co-ordinator said: "Several highly effective cancer drugs were first discovered as natural compounds. However, wonderful as Nature is, she is only half-way there when it comes to beating cancer. Often scientists can improve upon Nature's handiwork, by tweaking the chemical structure of these molecules -- just as Dr Fuchter has discovered with psammaplin A.
- Matthias G. J. Baud, Thomas Leiser, Franz-Josef Meyer-Almes, Matthew J. Fuchter. New synthetic strategies towards psammaplin A, access to natural product analogues for biological evaluation. Organic & Biomolecular Chemistry, 2011; 9 (3): 659 DOI: 10.1039/C0OB00824A
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