Discovery of Novel Leishmanicidal Drugs with Potential L-type Calcium Channel Blockage, Designed by Similarity-Based Virtual Screening Approaches

Calcium channel blockage as a therapeutic strategy for treatment of leishmaniasis has demonstrated a promising pathway of treatment for this pathology. In this work, virtual screening approaches have been performed in several databases of commercially available compounds in order to design novel leishmanicidal compounds with potential L-type calcium channel blockage. Several compounds were tested against Leishmania intracellular parasites, using High-Content Analyses Assays. Results have indicated two compounds with new chemotypes, which were able to kill the parasite, with moderate activity and high efficacy, without toxicity for the host. Compounds here discovered represent a very useful molecular simplification compared to the reference or control compound, amphotericin B, with suitable ADME/Tox properties and synthetic accessibility.