Identification of a Hit Series of Antileishmanial Compounds through the Use of Mixture-Based Libraries

From a screening campaign that included mixture-based libraries containing more than 6 million compounds, a lead series of bis-cyclic guanidines was identified as the most promising. Lead optimization resulted in the identification of potent (IC₅₀ < 500 nM) and selective compounds within this series as well as potent and selective monoguanidines

Synthesis and Activity of a New Series of Antileishmanial Agents

We have determined that tetrahydroindazoles such as <b>1</b> show potent activity against <i>Leishmania donovani</i>, the causative agent of leishmaniasis. While the Hsp90 activity and anticancer properties of <b>1</b> have previously been explored, we present here our efforts to optimize their activity against <i>L. donovani</i> via the synthesis of novel analogues designed to probe the hydrophobic pocket of the protozoan Hsp90 orthologue, specifically through the auspices of functionalization of an amine embedded into the scaffold