The Potential of N ‐Benzyl Spiro‐Oxindole Hydantoins as Antileishmanial Agents Against Leishmania infantum

ABSTRACT Leishmaniasis, caused by protozoa of the genus Leishmania remains a significant public health concern due to the high lethality of the visceral form if untreated. Current therapies have important limitations, including toxicity and the availability of only a single approved oral drug (miltefosine), highlighting the need for new therapeutic alternatives. N ‐benzyl spiro‐oxindole hydantoins represent promising antileishmanial candidates, combining benzyl, and oxindole cores, previously associated with anti‐ Leishmania activity, with hydantoin, a scaffold known for broad biological properties. The connection of these cores via a spiro carbon further enhances their structural potential. In this preliminary study these compounds were evaluated against Leishmania infantum promastigotes. The most active derivative exhibited an IC 50 of 37.85 µM and was subjected to docking studies to explore its possible mechanism of action. In silico predictions (SwissADME) suggested good oral bioavailability, and preliminary cytotoxicity assays in RAW 264.7 macrophages demonstrated high parasite selectivity, supporting their potential as novel antileishmanial agents.