Potential new class of antimalarials now open source

MMV provides promising compound series to researchers working in an open format
10 September 2013

Photo: © iStockphoto.com/Nicolas Loran

This week, MMV hands the triazolopyrazines and their key data over to Dr Mat Todd at the University of Sydney, where research on these potential antimalarials will continue for all the world to see as part of the Open Source Malaria project.

The triazolopyrazines have already demonstrated promising activity in laboratory models of malaria. They are thought to act by sending the malaria parasite’s ion balance into disarray. The compounds affect sodium homeostasis in Plasmodium falciparum and are believed to inhibit the sodium pump (PfATP4), which the parasite uses to expel sodium from its “body”. This inhibition causes an intolerable change in acidity inside the parasite leading to its death.

Since 2011, MMV has been working with scientists at the University of Sydney on an Open Source Drug Discovery programme (OSDD) for malaria. As the team conducts their research, details are posted online in a kind of 'electronic lab book'. Alerts then go out via social media whenever new data is added, and the team holds regular open web conferences. In this way, scientists from around the world are able to contribute to help solve problems and advance compounds.

“It’s one of the first initiatives to experiment with OSDD for malaria,” says Dr Jeremy Burrows, Head of Drug Discovery at MMV. “The project has clearly shown the willingness of scientists around the world to share knowledge and make a difference. It has also given us confidence to offer this new more advanced series to the programme.”

The triazolopyrazine series was identified from a high-throughput screen, performed by Prof. Vicky Avery at Eskitis, of a Pfizer compound library in collaboration with MMV. The series was then optimized, first with Pfizer and then with TCG Lifesciences under the leadership of Drs Mark Gardner, Mike Palmer, Tanya Parkinson, Michael Witty and Saumitra Sengupta.

As research on the series continues in the open, Prof. Kiaran Kirk from the Australian National University in Canberrra, a leading expert on P. falciparum sodium pumps (PfATP4), has agreed to join the project and provide his biological expertise.

“The triazolopyrazines are extremely interesting compounds and I think we can make fast progress with them as they are in a really healthy state,” says Mat. “Also, because the questions are quite specific, there are all sorts of interesting ways people can get involved. As a medicinal chemist, when you look at the compounds you just want to get stuck in and ask some questions.”

Drs David Waterson and Paul Willis from MMV will present posters on the series at the 17th Royal Society of Chemistry/Society of Chemical Industry Medicinal Chemistry Meeting in Cambridge (8th to 11th of September 2013).