Conclusions

Although the rate of malaria-related deaths has declined over the past few years, the progress is beginning to slow. With the recent emergence of resistance to current front-line artemisinin-based combination therapy, the need for the discovery of new antimalarials that can act through novel mechanisms of action has been pushed firmly to the top of the development agenda.

Over the past few years, high-throughput screens have identified a number of novel chemotypes that have since been developed into highly promising antimalarial candidates. Crucially, many of these compounds have demonstrated novel MoAs which are essential if future drugs are to succeed. This is wonderful progress and a testament to the hard work of the groups involved.

The discovery of these novel MoAs will pave the way for the development of future antimalarials. The exploration of further novel MoAs has become a possibility through the use of in vitro evolution and whole-genome analysis (IVIEWGA), which uses genome-base target discovery methods on compounds identified from the more common phenotypic screens [139]. In all such future development, creativity and ingenuity in the hit to lead campaigns will continue to be needed if people are to remain able to combat this formidable disease.

The pace of research progress is high, meaning updates to reviews such as this will always be needed (Additional file 3). It is proposed that derivatives of this open access review, combined with data in relevant databases such as the one currently in development by the Guide to Pharmacology [140], could aim to serve as more “living” sources of information for compounds in development and their potential targets.