Scientists Synthesize Unique Family of Anti-Cancer Compounds

February 12, 2010, Yale University

(PhysOrg.com) -- Yale University scientists have streamlined the process for synthesizing a family of compounds with the potential to kill cancer and other diseased cells, and have found that they represent a unique category of anti-cancer agents. Their discovery appears in this week’s online edition of the Journal of the American Chemical Society.

The team studied a family of compounds known as the kinamycins, which are naturally produced by bacteria during metabolism and are known for their potent toxicity. For years scientists have guessed that a core structure common to the different compounds within the group was responsible for this toxicity. Until now, chemists could not study the core structure because there was no simple way to create it in the laboratory.

Now the Yale team has developed a new method to recreate this structure that allows them to synthesize the kinamycins with much greater efficiency than previously possible. While scientists have produced kinamycins in the laboratory in the past, the Yale team was able to halve the number of steps required to go from simple, easily obtainable precursors to the complete molecule—from 24 down to 12.

“By shortening the synthesis we can now prepare these molecules in the quantities required for further studies, including animal studies and even clinical trials,” said Seth Herzon, assistant professor of chemistry and lead author of the study.

Working with researchers at the Yale School of Medicine and the Yale Chemical Genomics Screening Facility, the team has begun testing several of the compounds against cancer cells, with promising preliminary results. Next, they will work to understand the exact mechanism that makes the compounds—which are benign on their own—highly toxic once they penetrate cells.

“The key to success will be whether we can develop selectivity—whether we can kill cancer cells in the presence of non-cancerous tissue,” Herzon said. “Based on what we already know about the chemical reactivity of these molecules, I’m optimistic we can do this.”

The reactive core of the kinamycins also plays a key role in another compound the team is studying, called lomaiviticin A, which is even more toxic and could prove even more effective in destroying . “Lomaiviticin A is the big fish. It’s more potent than the kinamycins, but it’s also much harder to synthesize,” Herzon said.

Both the kinamycins and lomaiviticin A are unique in their toxicity profiles, Herzon said, representing a new category of anti-cancer agents.

“There’s no close analogy to draw from to predict how these molecules will behave, which will make it especially interesting to see where this research takes us,” Herzon said. “This research involves a lot of exciting chemistry, but it also has real applications in biology and human medicine.”

Other authors of the study include Christina Woo, Liang Lu, Shivajirao Gholap and Devin Smith, all of Yale University. Funding for this research was provided by Yale University and Eli Lilly.

Video: Watch as one of the kinamycin compounds synthesized by Yale researchers destroys ovarian cancer cells (the spherical objects) in less than 48 hours in lab tests.

More information: DOI:10.1021/ja910769j

Related Stories

Recommended for you

Lab-grown 'mini tumours' could personalise cancer treatment

February 23, 2018
Testing cancer drugs on miniature replicas of a patient's tumour could help doctors tailor treatment, according to new research.

Study tracks evolutionary transition to destructive cancer

February 23, 2018
Evolution describes how all living forms cope with challenges in their environment, as they struggle to persevere against formidable odds. Mutation and selective pressure—cornerstones of Darwin's theory—are the means ...

Researchers use a molecular Trojan horse to deliver chemotherapeutic drug to cancer cells

February 23, 2018
A research team at the University of California, Riverside has discovered a way for chemotherapy drug paclitaxel to target migrating, or circulating, cancer cells, which are responsible for the development of tumor metastases.

An under-the-radar immune cell shows potential in fight against cancer

February 23, 2018
One of the rarest of immune cells, unknown to scientists a decade ago, might prove to be a potent weapon in stopping cancer from spreading in the body, according to new research from the University of British Columbia.

Putting black skin cancer to sleep—for good

February 22, 2018
An international research team has succeeded in stopping the growth of malignant melanoma by reactivating a protective mechanism that prevents tumor cells from dividing. The team used chemical agents to block the enzymes ...

Cancer risk associated with key epigenetic changes occurring through normal aging process

February 22, 2018
Some scientists have hypothesized that tumor-promoting changes in cells during cancer development—particularly an epigenetic change involving DNA methylation—arise from rogue cells escaping a natural cell deterioration ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.