Leishmaniasis is a neglected tropical disease (NTD) transmitted through the bites of infected female phlebotomine sandflies endemic in Africa, the Americas, South-East Asia, and Eastern Mediterranean that threatens an estimated one billion.
Leishmaniasis is a complex vector-borne disease, caused by more than 20 species of the protozoan genus Leishmania, and associated with clinical manifestations ranging from relatively benign localized skin ulcers to a systemic disease, causing severe damage to visceral organs that is fatal if left untreated. The different forms of the disease are categorized as visceral (VL), cutaneous (CL), mucocutaneous, and post-kala-azar dermal (PKDL) leishmaniasis.
Current treatment options are restricted and associated with significant limitations including variable efficacy, serious toxicities, lengthy treatments, with all but miltefosine requiring supervised intravenous or intramuscular administration. Thus, there is an urgent need for new, effective, safe, and convenient treatments.
This presentation describes the discovery and optimization of a novel class of highly potent anti-leishmanials based on substituted pyridine-2-sulfonamides. Their in vitro efficacy profile and effects in in vivo models of VL will be described.