title: Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights.
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
  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.
authors.affiliation: Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Eduardo H G
authors.initials: EHG
authors.lastname: da Cruz
authors.affiliation: 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.
authors.forename: Molly A
authors.initials: MA
authors.lastname: Silvers
authors.affiliation: Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Guilherme A M
authors.initials: GAM
authors.lastname: Jardim
authors.affiliation: Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Jarbas M
authors.initials: JM
authors.lastname: Resende
authors.affiliation: National Laboratory of Experimental Oncology, Department of Physiology and Pharmacology, Federal University of Ceará, CEP 60180-900, Fortaleza, CE, Brazil.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Cavalcanti
authors.affiliation: National Laboratory of Experimental Oncology, Department of Physiology and Pharmacology, Federal University of Ceará, CEP 60180-900, Fortaleza, CE, Brazil.
authors.forename: Igor S
authors.initials: IS
authors.lastname: Bomfim
authors.affiliation: 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.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pessoa
authors.affiliation: Institute of Physics, University of São Paulo, 13560-160, São Carlos, SP, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: de Simone
authors.affiliation: Department of Chemistry, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Giancarlo V
authors.initials: GV
authors.lastname: Botteselle
authors.affiliation: Department of Chemistry, Federal University of Santa Catarina, 88040-900, Florianópolis, SC, Brazil.
authors.forename: Antonio L
authors.initials: AL
authors.lastname: Braga
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India.
authors.forename: Divya K
authors.initials: DK
authors.lastname: Nair
authors.affiliation: Department of Chemistry, Indian Institute of Technology Bombay, Mumbai, 400 076, India.
authors.forename: Irishi N N
authors.initials: INN
authors.lastname: Namboothiri
authors.affiliation: 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.
authors.forename: David A
authors.initials: DA
authors.lastname: Boothman
authors.affiliation: Institute of Exact Sciences, Department of Chemistry, Federal University of Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil. Electronic address: eufranio@ufmg.br.
authors.forename: Eufrânio N
authors.initials: EN
authors.lastname: da Silva Júnior
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D016227:Benzoquinones / Q000737:chemistry*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D010084:Oxidation-Reduction; D012643:Selenium / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D014230:Triazoles; C004532:quinone; D012643:Selenium
keywords: Chalcogens; Click chemistry; Quinone; Selenium; β-Lapachone