Synthesis and anti-Trypanosoma cruzi activity of naphthoquinone-containing triazoles: Electrochemical studies on the effects of the quinoidal moiety |
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Authors: | Emilay B.T. Diogo Gleiston G. Dias Bernardo L. Rodrigues Tiago T. Guimarães Wagner O. Valença Celso A. Camara Ronaldo N. de Oliveira Mauro G. da Silva Vitor F. Ferreira Yen Galdino de Paiva Marilia O.F. Goulart Rubem F.S. Menna-Barreto Solange L. de Castro Eufrânio N. da Silva Júnior |
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Affiliation: | 1. Instituto de Ciências Exatas, Departamento de Química, UFMG, 31270-901 Belo Horizonte, MG, Brazil;2. Núcleo de Pesquisas de Produtos Naturais, UFRJ, 21941-971 Rio de Janeiro, RJ, Brazil;3. Departamento de Ciências Moleculares, UFRPE, 52171-900 Recife, PE, Brazil;4. Universidade Federal de Pernambuco, UFPE, 50670-901 Recife, PE, Brazil;5. Instituto de Quí?mica, UFF, 24020-150 Niterói, RJ, Brazil;6. Instituto de Química e Biotecnologia, UFAL, Tabuleiro do Martins, 57072-970 Maceió, AL, Brazil;7. Laboratório de Biologia Celular, IOC, FIOCRUZ, 21045-900 Rio de Janeiro, RJ, Brazil |
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Abstract: | In our continued search for novel trypanocidal compounds, twenty-six derivatives of para- and ortho-naphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17–24, 28–30 and 36–38 are described herein for the first time. Three of these novel compounds (28–30) were found to be more potent than the standard drug benznidazole, with IC50/24 h values between 6.8 and 80.8 μM. Analysis of the toxicity to heart muscle cells led to LC50/24 h of <125, 63.1 and 281.6 μM for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent. |
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Keywords: | Lapachol β-Lapachone Quinone Chagas disease Trypomastigote Click chemistry Electrochemical parameters |
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