Navigation Links
Scientists synthesize long-sought-after anticancer agent
Date:1/31/2011

New Haven, Conn.A team of Yale University scientists has synthesized for the first time a chemical compound called lomaiviticin aglycon, leading to the development of a new class of molecules that appear to target and destroy cancer stem cells.

Chemists worldwide have been interested in lomaiviticin's potential anticancer properties since its discovery in 2001. But so far, they have been unable to obtain significant quantities of the compound, which is produced by a rare marine bacterium that cannot be easily coaxed into creating the molecule. For the past decade, different groups around the world have been trying instead to synthesize the natural compound in the lab, but without success.

Now a team at Yale, led by chemist Seth Herzon, has managed to create lomaiviticin aglycon for the first time, opening up new avenues of exploration into novel chemotherapies that could target cancer stem cells, thought to be the precursors to tumors in a number of different cancers including ovarian, brain, lung, prostate and leukemia. Their discovery appears online today in the Journal of the American Chemical Society.

"About three quarters of anticancer agents are derived from natural products, so there's been lots of work in this area," Herzon said. "But this compound is structurally very different from other natural products, which made it extremely difficult to synthesize in the lab."

In addition to lomaiviticin aglycon, Herzon's team also created smaller, similar molecules that have proven extremely effective in killing ovarian stem cells, said Gil Mor, M.D., a researcher at the Yale School of Medicine who is collaborating with Herzon to test the new class of molecules' potential as a cancer therapeutic.

The scientists are particularly excited about lomaiviticin aglycon's potential to kill ovarian cancer stem cells because the disease is notoriously resistant to Taxol and Carboplatin, two of the most common chemotherapy drugs. "Ovarian cancer has a high rate of recurrence, and after using chemotherapy to fight the tumor the first time, you're left with resistant tumor cells that tend to keep coming back," Mor explained. "If you can kill the stem cells before they have the chance to form a tumor, the patient will have a much better chance of survival and there aren't many potential therapies out there that target cancer stem cells right now."

Herzon's team, which managed to synthesize the molecule in just 11 steps starting from basic chemical building blocks, has been working on the problem since 2008 and spent more than a year on just one step of the process involving the creation of a carbon-carbon bond. It was an achievement that many researchers deemed impossible, but while others tried to work around having to create that bond by using other techniques, the team's persistence paid off.

"A lot of blood, sweat and tears went into creating that bond," Herzon said. "After that, the rest of the process was relatively easy."

Next, the team will continue to analyze the compound to better understand what's happening to the stem cells at the molecular level. The team hopes to begin testing the compounds in animals shortly.

"This is a great example of the synergy between basic chemistry and the applied sciences," Herzon said. "Our original goal of synthesizing this natural product has led us into entirely new directions that could have broad impacts in human medicine."


'/>"/>

Contact: Suzanne Taylor Muzzin
suzanne.taylormuzzin@yale.edu
203-432-8555
Yale University
Source:Eurekalert

Related biology news :

1. Scientists climb Mt. Everest to explain how hearts adapt and recover from low oxygen
2. Scripps Research scientists convert skin cells to beating heart cells
3. Scripps Research scientists reveal key mechanism governing nicotine addiction
4. Scientists determine what makes an orangutan an orangutan
5. Scientists link protein to the insulation of the nervous systems wiring
6. Scientists grow human liver tissue to be used for transplantation
7. Scientists reveal complete structure of HIVs outer shell
8. Scientists: Big city life may alter green attitudes
9. Scientists find the master switch for key immune cells in inflammatory diseases
10. MU scientists find new farming method to reduce greenhouse gases, increase farm yields
11. 7 CAMH scientists win Young Investigator awards focused on breakthrough research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/28/2016)... SAN FRANCISCO and BANGALORE, India ... part of EdgeVerve Systems, a product subsidiary of Infosys (NYSE: ... service provider, today announced a global partnership that ... convenient way to use mobile banking and payment services. ... Mobility is a key innovation area for financial services, but ...
(Date:4/26/2016)... and LONDON , ... Finacle, part of EdgeVerve Systems, a product subsidiary ... Onegini today announced a partnership to integrate the ...      (Logo: http://photos.prnewswire.com/prnh/20151104/283829LOGO ) ... provide their customers enhanced security to access and ...
(Date:4/19/2016)... 20, 2016 The new GEZE ... compact web-based "all-in-one" system solution for all door components. ... or the door interface with integration authorization management system, ... systems. The minimal dimensions of the access control and ... building installations offer considerable freedom of design with regard ...
Breaking Biology News(10 mins):
(Date:5/18/2016)... Calif. (PRWEB) , ... May 18, 2016 , ... ... awarded the Luis Villalobos Award to Cognition Therapeutics at the annual ACA Summit last ... company that is financed by one of ACA’s member angel groups. It is the ...
(Date:5/18/2016)... , May 18, 2016 The Biotech ... does not mean that there are no opportunities ahead. Today, ... Inc. (NASDAQ: THLD ), Seattle Genetics Inc. (NASDAQ: ... ), and Ophthotech Corp. (NASDAQ: OPHT ). Sign ... at: http://www.activewallst.com/ Threshold Pharmaceuticals ...
(Date:5/18/2016)... ... 18, 2016 , ... Every day, more than 5,400 ER ... Costing more than $56 billion in direct costs annually, asthma remains a critical ... the suffering associated with uncontrolled asthma can be overwhelmingly disproportionate and better managed,” ...
(Date:5/18/2016)... ... ... Ryan Benton was diagnosed with Duchenne Muscular Dystrophy (DMD) at the age ... DMD is a relatively common progressive genetic disorder, which causes aggressive deterioration of the ... He met with the founder of the Stem Cell Institute in Panama ...
Breaking Biology Technology: