Relationship between Electrochemical Parameters, Cytotoxicity Data against Cancer Cells of 3-Thio-Substituted Nor-Beta-Lapachone Derivatives. Implications for Cancer Therapy

Author(s)

de Paiva, Yen G. ^{[1, 2]} ; Silva, Thaissa L. ^{[1, 3]} ; Xavier, Andre F. A. ^[1] ; Cardoso, Mariana F. C. ^[4] ; da Silva, Fernando C. ^[4] ; Silva, Maria F. S. ^[5] ; Pinheiro, Daniel P. ^[5] ; Pessoa, Claudia ^{[5, 6]} ; Ferreira, Vitor F. ^[7] ; Goulart, Marilia O. F. ^[1]

Affiliation

^[1] Univ Fed Alagoas, Inst Quim & Biotecnol, BR-57072970 Maceio, AL - Brazil

^[2] Univ Fed Paraiba, DSE, CCEN, Cidade Univ S-N, Castel Branco 3, BR-58051085 Joao Pessoa, Paraiba - Brazil

^[3] Univ Fed Alagoas, Nucleo Ciencias Exatas NCEx, Campus Arapiraca, BR-57309005 Arapiraca, AL - Brazil

^[4] Univ Fed Fluminense, Dept Quim Organ, Inst Quim, Campus Valonguinho, BR-24020150 Niteroi, RJ - Brazil

^[5] Univ Fed Ceara, Lab Oncol Expt, Dept Fisiol & Farmacol, BR-60430275 Fortaleza, Ceara - Brazil

^[6] Fundacao Oswaldo Cruz Fiocruz Ceara, BR-60175047 Fortaleza, Ceara - Brazil

^[7] Univ Fed Fluminense, Dept Tecnol Farmaceut, Fac Farm, BR-24241002 Niteroi, RJ - Brazil

• Document type: Journal article
• Source: Journal of the Brazilian Chemical Society; v. 30, n. 3, SI, p. 658-672, MAR 2019.
• Web of Science Citations: 1

Abstract

Electrochemical methods are powerful in the characterization and design of redox-modulating agents. We, herein, report the electrochemical investigation, in aprotic medium, of eleven synthetic 3-thio-substituted-nor-beta-lapachones, along with the determination of cytotoxic activity and correspondent selectivity index, against several cancer cell lines and one normal cell. Four of the quinones are novel compounds. The redox behavior is representative of two independent systems: the easy reduction of the quinone moiety and, at far more negative potential, the reductive cleavage of the C-S-C bonding; and the anodic part controlled by the oxidation of the sulfur moiety. The compounds have shown relevant cytotoxic activity, with emphasis on 3-phenyl-thio-2,2-dimethyl-2,3-dihydronaphtho {[}1,2-b]furan-4,5-dione (compound 2), which mechanism of molecular action was shown to be related to reactive oxygen species (ROS) release. Despite the absence of a linear correlation, there is a trend: the majority of the thionaphthoquinones, with values of first wave reduction potential, less negative than -0.65 V, were active. The less electrophilic compound (3-(cyclohexylthio)-2,2-dimethyl-2,3-dihydronaphtho{[}1,2-b]furan-4,5-di one, cyclohexyl derivative) is also the less cytotoxic toward cancer cells. Agents containing chalcogens and quinones can be used to attack entities with a disturbed redox balance. (AU)

• FAPESP's process: 14/50867-3 - INCT 2014: National Institute of Science and Technology in Bioanalysis
• Grantee: Marco Aurelio Zezzi Arruda
• Support Opportunities: Research Projects - Thematic Grants