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

Eur J Med Chem. 2022 Dec 5:243:114687. doi: 10.1016/j.ejmech.2022.114687.

Ingrid C Chipoline ¹, Beatrice F A B Brasil ², José S S Neto ³, Marilia Valli ⁴, Renata Krogh ⁵, Arthur R Cenci ⁶, Kerolain F Teixeira ⁶, Eduardo Zapp ⁷, Daniela Brondani ⁸, Leonardo L G Ferreira ⁹, Adriano D Andricopulo ¹⁰, Aldo S de Oliveira ¹¹, Vanessa Nascimento ¹²

Affiliations

1 SupraSelen Laboratory, Department of Chemistry, Federal University Fluminense, Institute of Chemistry, Campus do Valonguinho, 24020-141, Niterói-RJ, Brazil. Electronic address: [email protected].
2 SupraSelen Laboratory, Department of Chemistry, Federal University Fluminense, Institute of Chemistry, Campus do Valonguinho, 24020-141, Niterói-RJ, Brazil. Electronic address: [email protected].
3 Department of Chemistry, Federal University of Santa Catarina- Campus Florianopolis, Trindade, Florianopolis, SC, 88040-900, Brazil. Electronic address: [email protected].
4 Laboratory of Medicinal and Computational Chemistry (LQMC), Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar), São Carlos Institute of Physics (IFSC), University of São Paulo (USP), Av. João Dagnone, 1100, 13563-120, São Carlos, SP, Brazil. Electronic address: [email protected].
5 Laboratory of Medicinal and Computational Chemistry (LQMC), Center for Research and Innovation in Biodiversity and Drug Discovery (CIBFar), São Carlos Institute of Physics (IFSC), University of São Paulo (USP), Av. João Dagnone, 1100, 13563-120, São Carlos, SP, Brazil. Electronic address: [email protected].
6 Department of Exact Sciences & Education, Federal University of Santa Catarina, Campus of Blumenau, Joao Pessoa, 2750, Velha, Blumenau, SC, 89036-256, Brazil.
7 Department of Exact Sciences & Education, Federal University of Santa Catarina, Campus of Blumenau, Joao Pessoa, 2750, Velha, Blumenau, SC, 89036-256, Brazil. Electronic address: [email protected].
8 Department of Exact Sciences & Education, Federal University of Santa Catarina, Campus of Blumenau, Joao Pessoa, 2750, Velha, Blumenau, SC, 89036-256, Brazil. Electronic address: [email protected].
9 Department of Chemistry, Federal University of Santa Catarina- Campus Florianopolis, Trindade, Florianopolis, SC, 88040-900, Brazil. Electronic address: [email protected].
10 Department of Chemistry, Federal University of Santa Catarina- Campus Florianopolis, Trindade, Florianopolis, SC, 88040-900, Brazil. Electronic address: [email protected].
11 Department of Exact Sciences & Education, Federal University of Santa Catarina, Campus of Blumenau, Joao Pessoa, 2750, Velha, Blumenau, SC, 89036-256, Brazil. Electronic address: [email protected].
12 SupraSelen Laboratory, Department of Chemistry, Federal University Fluminense, Institute of Chemistry, Campus do Valonguinho, 24020-141, Niterói-RJ, Brazil. Electronic address: [email protected].

PMID: 36057237 DOI: 10.1016/j.ejmech.2022.114687

Abstract

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.

Keywords

Chagas disease; Chalcogen; DFT; Heterocycle; Selenides; Triazole.

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