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

doi: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

Eur J Med Chem. 2016 Oct 21:122:1-16. doi: 10.1016/j.ejmech.2016.06.019. Epub 2016 Jun 14.

Authors

Affiliations

¹ Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil.
² Departments of Pharmacology and Radiation Oncology, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX, 75390-8807, USA.
³ National Laboratory of Experimental Oncology, Department of Physiology and Pharmacology, Federal University of Ceará, CEP 60180-900, Fortaleza, CE, Brazil.
⁴ National Laboratory of Experimental Oncology, Department of Physiology and Pharmacology, Federal University of Ceará, CEP 60180-900, Fortaleza, CE, Brazil; Fiocruz-Ceará, CEP 60180-900, Fortaleza, CE, Brazil.
⁵ Institute of Physics, University of São Paulo, 13560-160, São Carlos, SP, Brazil.
⁶ Department of Chemistry, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
⁷ Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India.
⁸ Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil. Electronic address: [email protected].

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.

Keywords: Chalcogens; Click chemistry; Quinone; Selenium; β-Lapachone.

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / toxicity
Benzoquinones / chemistry*
Cell Death / drug effects
Cell Line, Tumor
Chemistry Techniques, Synthetic
Drug Design
Humans
Leukocytes, Mononuclear / drug effects
Oxidation-Reduction
Selenium / chemistry*
Structure-Activity Relationship
Triazoles / chemical synthesis*
Triazoles / chemistry*
Triazoles / pharmacology*
Triazoles / toxicity

Substances

Antineoplastic Agents
Benzoquinones
Triazoles
quinone
Selenium

Abstract

MeSH terms

Substances

Grants and funding