Scientists succeed in synthesising promising anti-cancer fungal compound
Researchers at the Massachusetts Institute of Technology (MIT) have synthesised for the first time a complex fungal compound known as verticillin A, discovered more than 50 years ago and long viewed as a potential anti-cancer agent, WAM reports.
Verticillin A has a highly intricate structure that has made it far more difficult to synthesise than related compounds, despite differing from them by only a few atoms.
“We have a much better appreciation for how those subtle structural changes can significantly increase the synthetic challenge,” said Mohammad Movassaghi, a Professor of Chemistry at MIT. “Now we have the technology where we can not only access them for the first time, more than 50 years after they were isolated, but also we can make many designed variants, which can enable further detailed studies.”
In tests in human cancer cells, a derivative of verticillin A showed particular promise against a type of pediatric brain cancer called diffuse midline glioma.
Movassaghi and Jun Qi, Associate Professor of Medicine at Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Centre and Harvard Medical School, are the senior authors of the study, published in the Journal of the American Chemical Society.
Verticillin A consists of two identical halves that must be precisely fused into a dimer with the correct three-dimensional arrangement — a key challenge that had prevented its synthesis for decades.
To build verticillin A, the researchers used a few tricks, switching up the order in which they added molecules and protecting fragile bonds from being broken during synthesis.
Their 16-step process, which 'unmasked' some of verticillin A's functional groups after its two halves had been brought together, gave the researchers the precise 3D structure they needed.
"What we learned was the timing of the events is absolutely critical," said Movassaghi. "We had to significantly change the order of the bond-forming events."
Now that verticillin A has been synthesised for the first time, the work to understand how it interacts with cancer and how it could be adapted into treatments can be taken to a whole new level.
"Natural compounds have been valuable resources for drug discovery, and we will fully evaluate the therapeutic potential of these molecules by integrating our expertise in chemistry, chemical biology, cancer biology, and patient care," Jun Qi said.
Earlier, it was reported that cancer death rates had declined in Kazakhstan in past five years.
