Leishmania donovani Dipeptidylcarboxypeptidase Inhibitor as a Potential Oral Treatment for Visceral Leishmaniasis.

Chemotherapy is the key intervention to control visceral leishmaniasis (VL), a neglected tropical disease. Current regimens include not only a few drugs but also present several drawbacks, including moderate to severe toxicity, cost, long-term administration, patient compliance, and growing drug resistance. Thus, the need for better treatment options against VL is a priority. In an endeavor to find an orally active and affordable antileishmanial agent, we evaluated the therapeutic potential of compounds belonging to the (2Z,2'Z)-3,3'-(ethane-1,2-diylbis(azanediyl))bis(1-(4-halophenyl)-6-hydroxyhex-2-en-1-ones) series, identified as inhibitor(s) of Leishmania donovani dipeptidylcarboxypeptidase, a novel drug target. Among them, compound 3c exhibited best in vivo antileishmanial efficacy via both intraperitoneal and oral routes. Therefore, the present study led to the identification of compound 3c as the lead candidate for treating VL.