scholarly journals Pyridazino-pyrrolo-quinoxalinium salts as highly potent and selective leishmanicidal agents targeting trypanothione reductase

Author(s):  
Héctor de Lucio ◽  
Javier García-Marín ◽  
Patricia Sánchez-Alonso ◽  
Juan Carlos García-Soriano ◽  
Miguel Ángel Toro ◽  
...  
2021 ◽  
Vol 18 (4) ◽  
pp. 398-418
Author(s):  
Vinícius Guimarães da Paixão ◽  
Samuel Silva da Rocha Pita

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. Objective: 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.


ChemMedChem ◽  
2007 ◽  
Vol 2 (12) ◽  
pp. 1708-1712 ◽  
Author(s):  
Bernhard Stump ◽  
Marcel Kaiser ◽  
Reto Brun ◽  
R. Luise Krauth-Siegel ◽  
François Diederich

ChemMedChem ◽  
2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Gianni Colotti ◽  
Andrea Ilari ◽  
Annarita Fiorillo ◽  
Paola Baiocco ◽  
Maria Agostina Cinellu ◽  
...  

Author(s):  
Olivia Teixeira ◽  
Pedro Lacerda ◽  
Thamires Quadros Froes ◽  
Maria Cristina Nonato ◽  
Marcelo Santos Castilho

2007 ◽  
Vol 22 (1) ◽  
pp. 71-75 ◽  
Author(s):  
Denise Barçante Castro-Pinto ◽  
Edson L. Silva Lima ◽  
Andrea S. Cunha ◽  
Marcelo Genestra ◽  
Rosa Maria De Léo ◽  
...  

2009 ◽  
Vol 28 (4) ◽  
pp. 330-335 ◽  
Author(s):  
Samuel Silva da Rocha Pita ◽  
José Jair Vianna Cirino ◽  
Ricardo Bicca de Alencastro ◽  
Helena Carla Castro ◽  
Carlos Rangel Rodrigues ◽  
...  

Author(s):  
Gildardo Rivera

Background: For decades, the quinoxaline 1,4-di-N-oxide ring has been considered a privileged structure to develop new antibacterial, antitumoural, and antiprotozoal agents, among others, however its mechanism of action is not clear. Objective : The main aim of this mini-review was to analyze the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives reported as antibacterial, antitumoural and antiprotozoal agents. Results : Initially, the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives against bacteria, tumoural cell lines, and parasites has been described as nonspecific, but recently, the results against different organisms have shown that these compounds have an inhibitory action on specific targets such as trypanothione reductase, triosephosphate isomerase, and other essential enzymes. Conclusion: In summary, quinoxaline 1,4-di-N-oxide is a scaffold to develop new anti-Mycobacterium tuberculosis, antitumoural and antiprotozoal agents, however, understanding the mechanism of action of quinoxaline 1,4-di-N-oxide derivatives in each microorganism could contribute to the development of new, and more potent selective drugs.


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