Yale University scientists have streamlined the process for synthesising a family of compounds that can potentially kill cancer and other diseased cells, representing a unique category of anti-cancer agents.
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 lab.
Now the Yale team has developed a new method to recreate this structure that allows them to synthesise the kinamycins with much greater efficiency than previously possible.
While scientists have produced kinamycins in the lab 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 at Yale, who led 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, said a Yale release.
“The key to success will be whether we can develop selectivity - whether we can kill cancer cells in the presence of non-cancerous tissue,” Mr. Herzon said. “Based on what we already know about the chemical reactivity of these molecules, I’m optimistic we can do this.”
Their discovery appears in this week's online edition of the Journal of the American Chemical Society.
