Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights

Eduardo H G Da Cruz, Molly A. Silvers, Guilherme A M Jardim, Jarbas M. Resende, Bruno C. Cavalcanti, Igor S. Bomfim, Claudia Pessoa, Carlos A. De Simone, Giancarlo V. Botteselle, Antonio L. Braga, Divya K. Nair, Irishi N N Namboothiri, David A. Boothman, Eufrânio N. Da Silva Júnior

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Selenium-containing quinone-based 1,2,3-triazoles were synthesized using click chemistry, the copper catalyzed azide-alkyne 1,3-dipolar cycloaddition, and evaluated against six types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), PC3 (human prostate cells), SF295 (human glioblastoma cells), MDA-MB-435 (melanoma cells) and OVCAR-8 (human ovarian carcinoma cells). Some compounds showed IC50 values < 0.3 μM. The cytotoxic potential of the quinones evaluated was also assayed using non-tumor cells, exemplified by peripheral blood mononuclear (PBMC), V79 and L929 cells. Mechanistic role for NAD(P)H:Quinone Oxidoreductase 1 (NQO1) was also elucidated. These compounds could provide promising new lead derivatives for more potent anticancer drug development and delivery, and represent one of the most active classes of lapachones reported.

Original languageEnglish (US)
Pages (from-to)1-16
Number of pages16
JournalEuropean Journal of Medicinal Chemistry
Volume122
DOIs
StatePublished - Oct 21 2016

Fingerprint

Triazoles
Selenium
Oxidation-Reduction
Cells
Quinones
Alkynes
Azides
Cycloaddition
NAD
Copper
Oxidoreductases
Click Chemistry
Blood
HCT116 Cells
Carcinoma
Derivatives
Cycloaddition Reaction
Glioblastoma
benzoquinone
Inhibitory Concentration 50

Keywords

  • Chalcogens
  • Click chemistry
  • Quinone
  • Selenium
  • β-Lapachone

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Da Cruz, E. H. G., Silvers, M. A., Jardim, G. A. M., Resende, J. M., Cavalcanti, B. C., Bomfim, I. S., ... Da Silva Júnior, E. N. (2016). Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights. European Journal of Medicinal Chemistry, 122, 1-16. https://doi.org/10.1016/j.ejmech.2016.06.019

Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights. / Da Cruz, Eduardo H G; Silvers, Molly A.; Jardim, Guilherme A M; Resende, Jarbas M.; Cavalcanti, Bruno C.; Bomfim, Igor S.; Pessoa, Claudia; De Simone, Carlos A.; Botteselle, Giancarlo V.; Braga, Antonio L.; Nair, Divya K.; Namboothiri, Irishi N N; Boothman, David A.; Da Silva Júnior, Eufrânio N.

In: European Journal of Medicinal Chemistry, Vol. 122, 21.10.2016, p. 1-16.

Research output: Contribution to journalArticle

Da Cruz, EHG, Silvers, MA, Jardim, GAM, Resende, JM, Cavalcanti, BC, Bomfim, IS, Pessoa, C, De Simone, CA, Botteselle, GV, Braga, AL, Nair, DK, Namboothiri, INN, Boothman, DA & Da Silva Júnior, EN 2016, 'Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights', European Journal of Medicinal Chemistry, vol. 122, pp. 1-16. https://doi.org/10.1016/j.ejmech.2016.06.019
Da Cruz, Eduardo H G ; Silvers, Molly A. ; Jardim, Guilherme A M ; Resende, Jarbas M. ; Cavalcanti, Bruno C. ; Bomfim, Igor S. ; Pessoa, Claudia ; De Simone, Carlos A. ; Botteselle, Giancarlo V. ; Braga, Antonio L. ; Nair, Divya K. ; Namboothiri, Irishi N N ; Boothman, David A. ; Da Silva Júnior, Eufrânio N. / Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights. In: European Journal of Medicinal Chemistry. 2016 ; Vol. 122. pp. 1-16.
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