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.
European journal of medicinal chemistry. 2016 Jun 14 [Epub ahead of print]
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
Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil., 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., Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil., Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil., National Laboratory of Experimental Oncology, Department of Physiology and Pharmacology, Federal University of Ceará, CEP 60180-900, Fortaleza, CE, Brazil., National Laboratory of Experimental Oncology, Department of Physiology and Pharmacology, Federal University of Ceará, CEP 60180-900, Fortaleza, CE, Brazil., 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., Institute of Physics, University of São Paulo, 13560-160, São Carlos, SP, Brazil., Department of Chemistry, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil., Department of Chemistry, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil., Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India., Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India., 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., Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil. Electronic address: .