Similarity-based profiling of hydrazone-containing scaffolds active against leishmania amastigotes

This review explores the potential of hydrazone-containing scaffolds as antileishmanial agents, particularly targeting Leishmania amastigotes. Through a strategy focusing on the 3D electroshape properties of compounds, molecular alignment techniques were applied to analyze and compare structurally similar hydrazone derivatives. Rather than relying solely on traditional functional group analysis, this review adopts a shape-based profiling approach to uncover key structural features linked to antileishmanial activity. The review systematically compiles data on hydrazone-based compounds from various studies, with particular emphasis on those exhibiting significant activity against intracellular amastigotes. Structural comparisons were performed using molecular overlays, allowing the identification of promising compounds and their potential mechanisms of action. The selected hydrazone derivatives demonstrated noteworthy antileishmanial activity in vitro, with a focus on those active against the human phase of the parasite. By integrating both computational and experimental approaches, the review provides insights that may guide the optimization of hydrazone scaffolds for enhanced efficacy, bioavailability, and safety. Despite these promising findings, further investigation into the precise molecular targets of these compounds is necessary, as the exact mechanisms of action remain to be fully understood. Overall, this review highlights the potential of hydrazone-containing compounds as a valuable foundation for the development of new therapeutic agents against leishmaniasis, using a novel shape-based molecular alignment strategy to support drug discovery efforts.