Synthesis and evaluation of substrate analogue inhibitors of trypanothione reductase

Duyzend, Michael H.; Clark, Crystal T.; Simmons, Shayna L.; Johnson, Wade B.; Larson, Anna M.; Leconte, Aaron M.; Wills, Andrew W.; Ginder‐Vogel, Matthew; Wilhelm, April K.; Czechowicz, Josephine A.; Alberg, David G.

doi:10.3109/14756366.2011.604319

Cited by 13 publications

(4 citation statements)

References 46 publications

(53 reference statements)

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“…10). [76][77][78] They designed inhibitors 237-241 for TR containing hydrocarbon chains and synthesized from symmetric bis-amino acids (Fig. 11).…”

Section: Reviewmentioning

confidence: 99%

Synthesis and applications of symmetric amino acid derivatives

Tsukano,

Uchino,

Irie

2024

Org. Biomol. Chem.

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“…10). [76][77][78] They designed inhibitors 237-241 for TR containing hydrocarbon chains and synthesized from symmetric bis-amino acids (Fig. 11).…”

Section: Reviewmentioning

confidence: 99%

Synthesis and applications of symmetric amino acid derivatives

Tsukano,

Uchino,

Irie

2024

Org. Biomol. Chem.

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“…However, they in conjunction with a third one, displayed reversible competitive inhibition. Only one of them was displayed as the most potent inhibitor with a Ki value in the M order [346].…”

Section: -Natural Products Scaffolds [341-343] J-analogues Of Dethiot...mentioning

confidence: 99%

Targets and Patented Drugs for Chemotherapy of Chagas Disease in the Last 15 Years-Period

Duschak

2016

PRI

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In summary, loans on anti-Chagas disease agents focused to specific parasite targets as their metabolic pathways or specific enzymes will be summarized. Targets will also be specifically discussed. Patent literature collected and published from 2000 to 2015, alleging inhibitors for specific T. cruzi targets or trypanocidal activity was achieved over the search database from Delphion Research intellectual property network including international patents and the European patent office, Espacenet.

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“…License: CC BY 4.0 macrophages, generating reactive oxygen and nitrogen species such as superoxide anions, peroxynitrite, myeloperoxidase and hydrogen peroxide (Piacenza et al, 2013;Arias et al, 2017), these chemical molecules have high reactivity and their main consequence is the oxidation of biomolecules such as carbohydrates, lipids, nucleic acids and proteins; causing irreversible and severe damage that makes it impossible for trypanosomatids to replicate. T. cruzi confronts this environment with a sophisticated and efficient antioxidant machinery consisting of pathways linked between a thiol-dependent redox system: triparedoxin (TXN), an oxidoreductase that regulates low molecular weight dithiol-dependent oxide-reduction reactions, and NADPHdependent trypanothione reductase (TR), an enzyme that regenerates the reduced form of trypanothione (Duyzend et al, 2012;Piacenza et al, 2013;Arias et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

In silico screening based on chemoinformatics and molecular docking of trypanothione reductase inhibitors from Trypanosoma cruzi

Hernández Alba,

Galicia Galicia,

Retana Ugalde

et al. 2023

Preprint

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Chagas disease is caused by the parasite Trypanosoma cruzi. One of the two first-line drugs for treatment is nifurtimox, a nitrofuran that exhibits high toxicity. Therefore, the need arises to investigate new therapeutic options, and, in this sense, our objective was to study compounds that maintain the trypanocidal activity associated with the furan nucleus and by structural modification of substituents reduce their toxicity. In the following research work, a chemical library was formed using the databases PubChem, ChEMBL and ChemSpider, later a virtual screening was carried out with the chemoinformatic tools Way2Drug, molinspiration, DataWarrior and admetSAR obtaining the prediction of biological activity, physicochemical parameters, data of toxicity and pharmacokinetic properties, respectively. The last stage consisted of the molecular docking of the molecules at the active site of the trypanothione reductase protein of Trypanosoma cruzi, determining its binding energy and intermolecular interactions. Compounds NF-85, NF-150, NF-246 and NF-279 with potential anti-T. cruzi activity were identified, the four molecules had greater affinity for trypanothione reductase (-7.0, -7.2, -7.0 and -7.3 kcal / mol, respectively), compared to nifurtimox (-6.7 kcal / mol).

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Synthesis and evaluation of substrate analogue inhibitors of trypanothione reductase

Cited by 13 publications

References 46 publications

Synthesis and applications of symmetric amino acid derivatives

Synthesis and applications of symmetric amino acid derivatives

Targets and Patented Drugs for Chemotherapy of Chagas Disease in the Last 15 Years-Period

In silico screening based on chemoinformatics and molecular docking of trypanothione reductase inhibitors from Trypanosoma cruzi

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