Authors

B Baragana¹;  ¹ University of Dundee, UK

Discussion

Malaria is a devastating disease with over 214 million clinical cases every year. The World Health Organization (WHO) estimated 438000 deaths in 2015, predominantly amongst children and pregnant women in sub-Saharan Africa. Malaria in humans is caused by five Plasmodium species. The most pathogenic is P. falciparum which accounts for the majority of cases and deaths in Sub-Saharan Africa. P. vivax is the next most prevalent species, particularly in Southeast Asia and Central and South America. The malaria parasite has developed resistance to many of the current drugs available for treatment. To reduce the rate of development of resistance, World Health Organisation recommends an artemsisinin-based combination therapy (ACT) as first-line treatment for the majority of malaria cases. Worryingly there are now reported cases of clinical resistance to artemisinins. To support the current malaria eradication agenda, there are a number of needs for new anti-malarials: compounds with novel modes of action that are not cross-resistant to current drugs; single-dose treatments; compounds that kill gametocytes preventing transmission of the disease and treatments for relapsing malaria.
In my talk I will present the discovery and development of DDD107498, a potential new antimalarial agent. The starting point for this project was a phenotypic screen carried out against Plasmodium falciparum at the University of Dundee, UK. One of the identified series was optimized to a compound which fulfilled the Medicines for Malaria Venture criteria for a late lead compound. DDD107498 was extensively profiled in a large number of assays and has now been progressed into preclinical development with the aim of entering human clinical trials.[1] This pre-clinical candidate shows promise as a possible single-dose treatment in combination with another antimalarial and demonstrates both transmission blocking and chemoprevention potential.