Similarity-Based Profiling of Hydrazone-Containing Scaffolds Active Against <i>Leishmania</i> Amastigotes

This review explores the potential of hydrazone-containing scaffolds as anti-leishmanial agents with a particular focus on their activity against intracellular <i>Leishmania</i> amastigotes. Through a strategy centered on the 3D electroshape properties of compounds, structural analysis goes beyond the traditional functional group-based approach, employing molecular alignment techniques to identify key structural features associated with anti-leishmanial activity. This review systematically compiled data from previous studies, highlighting compounds with promising in vitro activity. Structural comparisons using molecular overlays have enabled the identification of promising compounds and the exploration of their potential mechanisms of action. The integration of computational and experimental approaches provides valuable insights into the rational optimization of hydrazone scaffolds with the aim of improving efficacy, bioavailability, and safety. However, complete elucidation of the precise molecular targets and mechanisms of action remains a crucial challenge for future research. In summary, this review highlights the potential of hydrazone-containing compounds as a basis for developing novel therapeutic agents against leishmaniasis by utilizing a shape-based molecular alignment strategy to drive drug discovery efforts.