Boston: Researchers at the Massachusetts Institute of Technology (MIT) have achieved a significant milestone by synthesising a complex fungal compound called verticillin A, which was discovered over 50 years ago and has long been considered a potential anti-cancer agent. Verticillin A is known for its highly intricate structure, which has made it much more challenging to synthesise compared to related compounds, despite differing from them by only a few atoms.
According to Emirates News Agency, Mohammad Movassaghi, a Professor of Chemistry at MIT, stated, “We have a much better appreciation for how those subtle structural changes can significantly increase the synthetic challenge.” He added that the advancement in technology now allows researchers to not only synthesise verticillin A for the first time but also create numerous designed variants, facilitating further detailed studies.
In laboratory tests using human cancer cells, a derivative of verticillin A demonstrated significant promise against diffuse midline glioma, a type of pediatric brain cancer. The study, showcasing this breakthrough, was authored by Movassaghi and Jun Qi, an Associate Professor of Medicine at Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Centre and Harvard Medical School. It was published in the Journal of the American Chemical Society.
The synthesis of verticillin A posed a formidable challenge due to its composition of two identical halves that must be precisely fused into a dimer with the correct three-dimensional arrangement. This complexity had prevented its synthesis for decades. The researchers employed innovative techniques, such as altering the order of molecular addition and protecting fragile bonds from breaking during synthesis, to overcome these challenges.
Their meticulous 16-step process involved “unmasking” some of verticillin A’s functional groups after its two halves were joined, achieving the precise 3D structure required. Movassaghi emphasized the importance of timing in the synthesis process, stating, “What we learned was the timing of the events is absolutely critical.”
With the successful synthesis of verticillin A, the researchers can now explore how the compound interacts with cancer cells and potentially develop it into effective treatments. Jun Qi highlighted the significance of natural compounds in drug discovery and expressed the team’s commitment to evaluating the therapeutic potential of verticillin A by integrating expertise across various disciplines, including chemistry, chemical biology, cancer biology, and patient care.