AsianScientist (Dec. 8, 2015) – A team of researchers from the University of Hong Kong (UHK) has successfully achieved the efficient synthesis of cortistatin A, a molecule which could help mitigate the growth of cancer tumors. Their results have been published in Chemistry — A European Journal.
Cancer is characterized by abnormal and unregulated cell growth, but tumors cannot grow larger than two millimetres unless they are accompanied by angiogenesis, which is a development of the blood vessel network needed to nourish the tumor and enable it to metastasize.
Thus, angiogenesis-inhibiting molecules could help mitigate the growth of cancer tumours. Currently, Avastin®, an anti-angiogenic drug, is in clinical use for the treatment a range of cancers.
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.
It is difficult to harvest Cortistatin A from natural sources, and thus laboratory synthesis could be beneficial. The research team, led by Professor Pauline Chiu from UHK’s Department of Chemistry, applied a (4+3) cycloaddition reaction which was developed and optimized in her lab to make a 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. 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,” said Chiu.
The impressive biological properties and complexity of the structure of cortistatin A have motivated many renowned chemists worldwide to synthesize this molecule. The efficient route that Chiu developed affords the highest total synthesis yield of cortistatin A reported in the world so far, according to the researchers.
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 to improve its efficacies toward drug development.
The article can be found at: Kuang et al. (2015) Formal Total Synthesis of (+)-Cortistatins A and J.
Source: The University of Hong Kong.
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