Vinícius Guimarães da Paixão and Samuel Silva da Rocha Pita* Pages 398 - 418 ( 21 )
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.
Leishmaniasis, Leishmania infantum, trypanothione reductase, natural products, biodiversity, virtual screening.
Laboratorio de Bioinformatica e Modelagem Molecular (LaBiMM), Pharmacy College, Federal University of Bahia (UFBA), Salvador, Laboratorio de Bioinformatica e Modelagem Molecular (LaBiMM), Pharmacy College, Federal University of Bahia (UFBA), Salvador