Navigation Links
Research update: Chemists find help from nature in fighting cancer

CAMBRIDGE, MA -- Inspired by a chemical that fungi secrete to defend their territory, MIT chemists have synthesized and tested several dozen compounds that may hold promise as potential cancer drugs.

A few years ago, MIT researchers led by associate professor of chemistry Mohammad Movassaghi became the first to chemically synthesize 11,11'-dideoxyverticillin, a highly complex fungal compound that has shown anti-cancer activity in previous studies. This and related compounds naturally occur in such small amounts that it has been difficult to do a comprehensive study of the relationship between the compound's structure and its activity research that could aid drug development, Movassaghi says.

"There's a lot of data out there, very exciting data, but one thing we were interested in doing is taking a large panel of these compounds, and for the first time, evaluating them in a uniform manner," Movassaghi says.

In the new study, recently published online in the journal Chemical Science, Movassaghi and colleagues at MIT and the University of Illinois at Urbana-Champaign (UIUC) designed and tested 60 compounds for their ability to kill human cancer cells.

"What was particularly exciting to us was to see, across various cancer cell lines, that some of them are quite potent," Movassaghi says.

Lead author of the paper is MIT postdoc Nicolas Boyer. Other authors are MIT graduate student Justin Kim, UIUC chemistry professor Paul Hergenrother and UIUC graduate student Karen Morrison.

Improving nature's design

Many of the compounds tested in this study, known as epipolythiodiketopiperazine (ETP) alkaloids, are naturally produced by fungi. Scientists believe these compounds help fungi prevent other organisms from encroaching on their territory.

In the process of synthesizing ETP natural products in their lab, the MIT researchers produced many similar compounds that they suspected might also 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 might be even more effective. "We can go in with far greater precision and test the hypotheses we're developing in terms of what portions of the molecules are most significant at retaining or enhancing biological activity," Movassaghi says.

Contact: Sarah McDonnell
Massachusetts Institute of Technology

Related medicine news :

1. U.S. Teen Birth Rates Highest in Rural Areas, Research Shows
2. Pessimism about the future may lead to longer, healthier life, research finds
3. Gut microbiota research: Pinpointing a moving target
4. Research suggests malaria can be defeated without a globally led eradication program
5. Researchers at the UH Cancer Center discover protein that may control the spread of cancer
6. Now hear this: Stanford researchers identify forerunners of inner-ear cells that enable hearing
7. Researchers explore PKC role in lung disease
8. Cleveland Clinic researcher receives grant to fund autism research
9. Bhatia honored by Southern Society for Pediatric Research
10. NIH awards $12.4 million grant to fund Henry Ford Hospital hypertension research
11. RWJF awards $1.9 million grant to PatientsLikeMe to create open research platform
Post Your Comments:
(Date:11/25/2015)... ... November 25, 2015 , ... ... preparing the perfect dish and pleasing the palates of attendees is of the ... a dish to a seasonal get-together, give these recipes a try this holiday ...
(Date:11/25/2015)... ... November 26, 2015 , ... ... European Union (EU), ANDI Pan African Centres of Excellence, and public R&D institutions, ... (UNON) for the opening of the 5th African Network for Drugs and Diagnostics ...
(Date:11/25/2015)... ... November 25, 2015 , ... Dental professionals who would ... OH , are invited to attend Dr. Mark Iacobelli’s Advanced Implant Mentoring (AIM) CE ... Cleveland, OH. , As the co-founders of Advanced Implant Mentoring (AIM), Dr. Iacobelli ...
(Date:11/25/2015)... ... November 25, 2015 , ... Smiles by Stevens is pleased ... moderate facial wrinkling. While many patients are aware of the benefits of Botox® in ... delivers to those suffering with discomfort, soreness, and pain as a result of Jaw ...
(Date:11/25/2015)... (PRWEB) , ... November 25, 2015 , ... “While riding ... an inventor, from Bronx, N.Y. “I thought there had to be a convenient and ... the PROTECTOR. , The PROTECTOR enables disabled individuals to safely travel during cold or ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... ) has ... Future Horizons and Growth Strategies in the ... Shares, Country Segment Forecasts, Competitive Intelligence, Emerging ... --> ) has announced the ... and Growth Strategies in the French Drugs ...
(Date:11/26/2015)... November 26, 2015 ... universitetssjukhus ser potential att använda SyMRI för ... för patienter med multipel skleros (MS) ... med SyntheticMR AB för att kunna använda ... sjukhuset. Med SyMRI kan man generera flera ...
(Date:11/26/2015)... India , November 26, 2015 ... --> adds ... Report" and "Investigation Report on China ... and 2021 forecasts data and information ... . ...
Breaking Medicine Technology: