Exploring Endoperoxides as Leishmanicidal Compounds

With advances in genomics, proteomics, and bioinformatics, identification of unique parasite-specific metabolic pathways has facilitated development of antileishmanial chemotherapeutics. In view of Leishmania parasites having a compromised antioxidant defense mechanism, induction of oxidative stress is a universal strategy adopted by conventional antileishmanial drugs with mitochondrial dysfunction being the major source of free radicals. However, a limitation is that mammalian mitochondria too are inhibited. Therefore, an attractive therapeutic option would be compounds like endoperoxides which owing to their unusual peroxide bridge mediate parasiticidal activity primarily via generation of free radicals. Accordingly, exploring the leishmanicidal potential of endoperoxides like artemisinin and ascaridole having established antimalarial and antihelminthic properties respectively, was the focus of this study. Leishmania proved to be a susceptible target for these free radical generating endoperoxides, making this therapeutic modality worthy of future pharmacological consideration.