Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research update: Chemists find help from nature in fighting cancer

28.02.2013
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.

The research was funded by the National Institute of General Medical Sciences.

Written by: Anne Trafton, MIT News Office

Sarah McDonnell | EurekAlert!
Further information:
http://www.mit.edu

Further reports about: ETP Movassaghi anti-cancer activity blood cell cancer cells single molecule uiuc

More articles from Life Sciences:

nachricht The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences

nachricht Transforming plant cells from generalists to specialists
07.12.2016 | Duke University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

NTU scientists build new ultrasound device using 3-D printing technology

07.12.2016 | Health and Medicine

The balancing act: An enzyme that links endocytosis to membrane recycling

07.12.2016 | Life Sciences

How to turn white fat brown

07.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>