Verticillin A Synthesised By MIT: First Complete Assembly Of Complex Anti-Cancer Fungal Compound

MIT researchers have, for the first time, chemically produced verticillin A, a complex fungal molecule discovered over 50 years ago and long studied as a possible anti-cancer agent. Synthetic access opens controlled testing and fine-tuned modification for oncology research.

The compound’s potential became clearer when a verticillin A derivative showed strong activity in laboratory tests on human cancer cells, especially against diffuse midline glioma, a severe pediatric brain tumour. This result supports renewed interest in natural products for targeted cancer therapy.

Verticillin A has two identical molecular halves that must join as a precise dimer with an exact three-dimensional shape. This demanding geometry, and only slight differences from related compounds, blocked chemists from preparing it in the laboratory for decades.

Mohammad Movassaghi, a Professor of Chemistry at MIT, explained how small changes in structure complicated the effort. "We have a much better appreciation for how those subtle structural changes can significantly increase the synthetic challenge," said Movassaghi. "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."

The team constructed verticillin A through a 16-step route that carefully controlled bond formation. They adjusted the sequence of chemical steps, shielded fragile bonds from damage, and later "unmasked" key functional groups after the two halves had been joined.

Describing this process, Movassaghi said, "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." This timing strategy allowed the exact 3D architecture required for biological studies.

verticillin A research collaboration and medical outlook

The study appears in the Journal of the American Chemical Society and is led by senior authors 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.

With synthetic verticillin A now available, researchers can examine how the molecule and its variants influence cancer pathways. Jun Qi highlighted the broader programme, stating, "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.

With inputs from WAM