Investigating the Potential of Primary Sulfonamides as Antimalarial Drug Leads

Abstract

Malaria remains one of the world’s most important infectious diseases causing over 600,000 deaths annually, mainly in African children under the age of five [1]. In the absence of a licenced vaccine, malaria prevention and treatment relies on drugs and vector control [1]. Unfortunately malaria parasite resistance has emerged to currently used antimalarial drugs, including the current gold standard artemisinin combination therapies (ACTs) [1-3]. Added to this, the majority of agents in the current antimalarial drug discovery and development portfolio are based on known antimalarial pharmacophores [4], which may compromise their widespread use due to potential issues of cross resistance. With only one new antimalarial chemical class (chemotype) presently under development, the spiroindolones [5], there is an urgent need to ensure that the antimalarial drug discovery pipeline is primed with new chemotypes, ideally with novel modes of action in order to combat resistance. In this thesis project this problem was addressed by investigating the antimalarial potential of primary sulfonamides (PS), a chemotype not currently used for malaria, but with a proven track record for treatment of other diseases, including glaucoma, renal disorders and epilepsy [6].