Similarity-based profiling of hydrazone-containing scaffolds active against leishmania amastigotes
hydrazone scaffolds, leishmaniasis, similarity-based, molecular alignment, drug discovery.
This review explores the potential of hydrazone-containing scaffolds as antileishmanial agents, with a special focus on their activity against intracellular amastigotes of Leishmania. Through a strategy centered on the 3D electroshape properties of the compounds, the structural analysis goes beyond the traditional functional group-based approach, utilizing molecular alignment techniques to identify key structural features associated with antileishmanial activity. Thus, this review has systematically compiled data from previous studies, highlighting compounds with promising in vitro activities and structural comparisons by molecular superimposition that allowed for the identification of promising compounds and the exploration of their possible mechanisms of action. The integration of computational and experimentais approaches has provided valuable insights for the rational optimization of hydrazone-containing scaffolds, aiming to improve efficacy, bioavailability, and safety. However, the complete elucidation of the molecular targets and mechanisms of action still represents a crucial challenge for future research. In summary, this review highlights the potential of hydrazone-containing compounds as a basis for the development of new therapeutic agents against leishmaniasis, utilizing a shape-based molecular alignment strategy to drive drug discovery efforts.