Background: Leishmania infantum causes the most lethal form of Leishmaniasis: Visceral
leishmaniasis. Current therapy for this disease is related to the development of drug-resistant
species and toxicity. Trypanothione Reductase (LiTR), a validated target for the drug discovery
process, is involved with parasites' thiol-redox metabolism.
Methods: In this study, through Virtual Screening employing two distinct Natural Products Brazilian
databases, we aimed to identify novel inhibitor scaffolds against LiTR.
Results: Thus, the “top 10” LiTR-ligand energies have been selected and their interaction profiles
into LiTR sites through the AuPosSOM server have been verified. Finally, Pred-hERG, Aggregator
Advisor, FAF-DRUGS, pkCSM and DataWarrior were employed and their results allowed us to
evaluate, respectively, the cardiotoxicity, aggregation capacity, presence of false-positive compounds
(PAINS) and their toxicities.
Conclusion: Three molecules that overcame the in silico pharmacokinetic analysis and have a
good interaction with LiTR, were chosen to use in vitro assays hoping that our computational results
reported here would aid the development of new anti-leishmanial compounds.