Anti-Cancer Drug Efficiently Synthesized In The Lab

Cortistatin A inhibits cancer tumors from growing blood vessels, but is difficult to harvest from nature. Now, researchers have fully synthesized it in high-yield quantities.

AsianScientist (Apr. 15, 2016) – A team of researchers led by Professor Pauline Chiu from the Department of Chemistry, the University of Hong Kong, has managed to synthesize cortistatin A, a molecule which could help slow the growth of cancer tumors, in the lab. The findings were published in Chemistry-A European Journal.

Cancer is a disease characterized by an abnormal and unregulated growth of cells. Nevertheless, cancer tumors cannot grow larger than two millimeters unless it is accompanied by angiogenesis—the development of a blood vessel network needed to nourish the tumor and enable it to spread to other parts of the body. Thus, angiogenesis-inhibiting molecules could help to slow the growth of cancer tumors.

Cortistatin A is a natural product isolated from an Indonesian marine sponge that has been shown to have potent anti-angiogenic activity at low dosages. Apart from being a lead compound in the development of anti-cancer therapies, a derivative of cortistatin A has also been found to be a powerful anti-HIV agent.

However, it is difficult to harvest cortistatin A from natural sources, and thus, laboratory synthesis is an alternative way to obtain quantities of it for further research and drug development.

The impressive biological properties and complexity of the structure of cortistatin A have motivated many renowned chemists worldwide to attempt to synthesize this molecule. The research team succeeded at doing so by applying a (4+3) cycloaddition reaction, which was developed and optimized in Chiu’s lab, to make the central seven-membered ring structure.

“The invention of new chemistry reactions is an extremely important field of research, because each new reaction is an enabling tool, and can open doors to the synthesis of many important molecules,” said Chiu.

“In this case, the cycloaddition reaction we developed is the key step in our strategy that enabled our synthesis of cortistatin A to be accomplished efficiently.”

The efficient route that Chiu developed affords the highest total synthesis yield of cortistatin A reported in the world so far. The yield exceeds that of a semi-synthetic route developed in the Scripps Research Institute, and is over seven-fold higher than the total synthesis developed at Harvard University.

Using this route, cortistatin A and its analogues can be more efficiently synthesized, to facilitate further medicinal chemistry research and future drug development.


The article can be found at: Kuang et al. (2016) Formal Total Synthesis of (+)-Cortistatins A and J.

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Source: University of Hong Kong; Photo: Shutterstock.
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