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

31 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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    Da Cruz, E. H. G., Silvers, M. A., Jardim, G. A. M., Resende, J. M., Cavalcanti, B. C., Bomfim, I. S., Pessoa, C., De Simone, C. A., Botteselle, G. V., Braga, A. L., Nair, D. K., Namboothiri, I. N. N., Boothman, D. A., & 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