Synthesis and investigation of the trypanocidal potential of novel 1,2,3-triazole-selenide hybrids

Synthesis and investigation of the trypanocidal potential of novel 1,2,3-triazole-selenide hybrids

Chagas Disease is caused by the protozoan Trypanosoma cruzi and is considered a tropical neglected disease by the World Health Organization (WHO). The main drugs used in the therapy of the disease are obsolete and, as a result, it still kills millions of people every year. Therefore, the development...

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Published in:European journal of medicinal chemistry Vol. 243; p. 114687
Main Authors: Chipoline, Ingrid C., Brasil, Beatrice F.A.B., Neto, José S.S., Valli, Marilia, Krogh, Renata, Cenci, Arthur R., Teixeira, Kerolain F., Zapp, Eduardo, Brondani, Daniela, Ferreira, Leonardo L.G., Andricopulo, Adriano D., de Oliveira, Aldo S., Nascimento, Vanessa
Format: Journal Article
Language:English
Published: Elsevier Masson SAS 05-12-2022
Subjects:
Chagas disease
Chalcogen
DFT
Heterocycle
Selenides
Triazole
HRMS
CD
Triazole
NMR
DFT
CV
Chalcogen
Chagas disease
NHE
Heterocycle
PAINS
Selenides
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Summary:Chagas Disease is caused by the protozoan Trypanosoma cruzi and is considered a tropical neglected disease by the World Health Organization (WHO). The main drugs used in the therapy of the disease are obsolete and, as a result, it still kills millions of people every year. Therefore, the development of new drugs is urgent, as is the research reported in this article, in which new triazole selenides were synthesized through a simple methodology and to evaluate their potential against T. cruzi, through a combination of in vitro and in silico assays. With the combination of two molecular scaffolds already known for this activity, sixteen new hybrid compounds were obtained, showing yields ranging from 40 to 90%, and their biological potentials were tested. Two of the evaluated hybrids showed potent trypanocidal activity (11m and 11n), comparable to the positive control benznidazole. Density functional theory (DFT) studies were correlated with cyclic voltammetry assays to investigate the LUMO energy, which demonstrated a correlation with the observed trypanocidal activity. These results are promising, considering 11m and 11n as hit compounds in the development of new antichagasic drugs. [Display omitted] •New 1,2,3-triazole-chalcogen hybrids were synthesized.•The hybrids were evaluated against T. cruzi, through a combination of in vitro and in silico assays.•The trypanocide assays revealed two promising compounds, 11m and 11n.•DFT and CV studies demonstrated a correlation with trypanocidal activity observed.•11m-n represent promising hit compounds in the discovery of new antichagasic drugs.
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ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2022.114687