MIT Chemists Synthesize Anticancer Compound Verticillin A
MIT chemists have produced verticillin A in the lab for the first time. This fungal molecule was identified over 50 years ago and has garnered attention for its potential as an anticancer agent.
Verticillin A is notoriously difficult too synthesize due to its intricate chemical architecture. It proved far more challenging to create than closely related compounds, differing by only a couple of atoms.
“We now have a much better understanding of how subtle structural changes can significantly increase the synthetic challenge,” says Mohammad Movassaghi, an MIT professor of chemistry.”We can now access these compounds for the first time,more than 50 years after their isolation,and create many designed variants for further study.”
lab tests using human cancer cells showed one verticillin A derivative was particularly effective against a pediatric brain cancer called diffuse midline glioma. Researchers emphasize that more testing is needed to determine if it might very well be used clinically.
Mohammad Movassaghi and Jun qi, an associate professor of medicine at Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School, are the senior authors of the study, published in the Journal of the American Chemical Society. walker Knauss PhD ’24 is the paper’s lead author.Xiuqi Wang,a medicinal chemist and chemical biologist at Dana-farber,and Mariella Filbin,research director in the Pediatric Neurology-Oncology Program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center,also contributed.
Why This Fungal Molecule Was So Hard to Make
Researchers first isolated verticillin A from fungi in 1970. Fungi use this compound to defend themselves from pathogens. verticillin A and similar fungal molecules have been explored for potential anticancer and antimicrobial activity,but their complexity has hindered synthesis.
In 2009, Movassaghi’s lab synthesized (+)-11,11′-dideoxyverticillin A, a compound closely related to verticillin A.This molecule contains 10 rings and eight stereogenic centers – carbon atoms each connected to four different chemical groups. Correct positioning, or stereochemistry, of these groups is crucial.
Despite that earlier success, verticillin A remained elusive. The key difference between verticillin A and (+)-11,11′-dideoxyverticillin A is two oxygen atoms. These seemingly small changes dramatically increased the difficulty of synthesis.