Synthesising natural antimalarial drugs

Posted 5 May 2017

Medicinal chemists from UNSW, Dr Hamish Toop and Associate Professor Jonathan Morris, have synthesised a potent antimalarial compound naturally produced by a rare tropical plant.

For decades, researchers have known about the therapeutic properties of a family of molecules produced by Dioncophyllum thollonii. But due to the low concentrations within the plant, they could not extract enough of the compounds for further analysis, let alone for clinical use.

Morris and Toop developed the first strategy to efficiently synthesise one of the compounds, Dioncophylline E, in the laboratory from scratch, using readily available chemicals.

“We’ve made the exact compound that the plant makes, but completely synthetically,” says Toop, a postdoctoral researcher in the Morris Group.

Total synthesis of this drug family has eluded chemists, until now. Morris and Toop devised a strategy to form crucial bonds efficiently to build the final product, and they report this strategy in Angewandte Chemie Internatinoal Edition, the leading general chemistry journal on 4 May 2017.

Wide-spread resistance in malaria parasites means there is an urgent need for new therapeutic compounds to control the spread of disease, which is transmitted by mosquitos.

This compound has been previously shown to be highly effective for treating malaria, without the toxicity associated with many existing antimalarial drugs. It is effective against the deadliest form of malaria, caused by Plasmodium falciparum, a species rapidly developing resistance to most antimalarial agents currently on the market.

The synthesis method developed by the UNSW team could be adapted to synthesise other members of the family of molecule produced by the same plant, which could have medicinal properties for other diseases.