Novel Scaffolds for Leishmania infantum Trypanothione Reductase Inhibitors Derived from Brazilian Natural Products Biodiversity

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Author(s): Vinícius Guimarães da Paixão, Samuel Silva da Rocha Pita*

Journal Name: Anti-Infective Agents
Anti-Infective Agents in Medicinal Chemistry

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Background: Leishmania infantum causes the most lethal form of Leishmaniasis: Visceral leishmaniasis. Current therapy for this disease is related with both the development of drug-resistant species and toxicity. Trypanothione Reductase (LiTR), a validated target for drug discovery process, is involved with parasite’s thiol‐redox metabolism.

Objective: In this study, through Virtual Screening studies employing two distinct Natural Products Brazilian databases, we aimed to identify novel inhibitor scaffolds against LiTR.

Methods and Results: Thus, we selected the “top 10” LiTR-ligand energies and verified their interaction profiles into LiTR sites through the AuPosSOM server. 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 its toxicity.

Conclusion: Three molecules that overcomes the in silico pharmacokinetic analysis and has a good interaction with LiTR were chose to in vitro assays hoping that our computational results reported here would aid the development of new anti-leishmanial compounds.

Keywords: Leishmaniasis, Leishmania infantum, Trypanothione Reductase, Natural Products, Biodiversity, Virtual Screening

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(E-pub Ahead of Print)
DOI: 10.2174/2211352518666200131121308

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