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Research update: Chemists find help from nature in fighting cancer
Date:2/27/2013

lso have anti-cancer activity. For the new study, they created even more compounds by systematically varying the natural structures adding or removing certain chemical groups from different locations.

The researchers tested 60 compounds against two different human cancer cell lines cervical cancer and lymphoma. Then they chose the best 25 to test against three additional lines, from lung, kidney and breast tumors. Overall, dimeric compounds those with two ETP molecules joined together appeared to be more effective at killing cancer cells than single molecules (known as monomers).

The structure of an ETP natural product typically has at least one set of fused rings containing one or more sulfur atoms that link to a six-member ring known as a cyclo-dipeptide. The researchers found that another key to tumor-killing ability is the arrangement and number of these sulfur atoms: Compounds with at least two sulfur atoms were the most effective, those with only one sulfur atom were less effective, and those without sulfur did not kill tumor cells efficiently.

Other rings typically have chemical groups of varying sizes attached in certain positions; a key position is that next to the ETP ring. The researchers found that the larger this group, the more powerful the compound was against cancer.

The compounds that kill cancer cells appear to be very selective, destroying them 1,000 times more effectively than they kill healthy blood cells.

The researchers also identified sections of the compounds that can be altered without discernably changing their activity. This is useful because it could allow chemists to use those points to attach the compounds to a delivery agent such as an antibody that would target them to cancer cells, without impairing their cancer-killing ability.

Complex synthesis

Now that they have some initial data, the researchers can use their findings to design additional compounds that
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Contact: Sarah McDonnell
s_mcd@mit.edu
617-827-7637
Massachusetts Institute of Technology
Source:Eurekalert

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