Growth inhibitory effects of 3′-nitro-3-phenylamino nor-beta-lapachone against HL-60: A redox-dependent mechanism

被引：43

作者：

Araujo, A. J. ^{[1
]}

de Souza, A. A. ^{[2
]}

da Silva Junior, E. N. ^{[3
,4
]}

Marinho-Filho, J. D. B. ^{[1
]}

de Moura, M. A. B. F. ^{[2
]}

Rocha, D. D. ^{[1
]}

Vasconcellos, M. C. ^{[5
]}

Costa, C. O. ^{[2
]}

Pessoa, C. ^{[1
]}

de Moraes, M. O. ^{[1
]}

Ferreira, V. F. ^{[6
]}

de Abreu, F. C. ^{[2
]}

Pinto, A. V. ^{[4
]}

Montenegro, R. C. ^{[7
]}

Costa-Lotufo, L. V. ^{[1
]}

Goulart, M. O. F. ^{[2
,8
]}

机构：

[1] Univ Fed Ceara, Dept Fisiol & Farmacol, BR-60430270 Fortaleza, CE, Brazil

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

[3] Univ Fed Minas Gerais, Dept Quim, Inst Ciencias Exatas, BR-31270901 Belo Horizonte, MG, Brazil

[4] Univ Fed Rio de Janeiro, Nucleo Pesquisas Prod Nat, BR-21941971 Rio De Janeiro, RJ, Brazil

[5] Univ Fed Amazonas, Fac Ciencias Farmaceut, BR-69010300 Manaus, AM, Brazil

[6] Univ Fed Fluminense, Inst Quim, BR-24020150 Niteroi, RJ, Brazil

[7] Fed Univ Para, Inst Ciencias Biol, BR-66075110 Belem, PA, Brazil

[8] Univ Estadual Campinas, Inst Nacl Ciencia & Tecnol Bioanalit, BR-13083970 Campinas, SP, Brazil

来源：

TOXICOLOGY IN VITRO | 2012年 / 26卷 / 04期

关键词：

Apoptosis; Cytotoxicity; DNA sensors; Nitroquinone; Nor-beta-lapachone; Bioelectrochemistry; OXIDATIVE STRESS; RADICAL-ANIONS; OXYGEN INTERACTION; HYDROGEN-PEROXIDE; ALPHA-LAPACHONE; LEUKEMIA HL-60; CANCER-CELLS; DNA-DAMAGE; APOPTOSIS; DERIVATIVES;

D O I：

10.1016/j.tiv.2012.02.003

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 [卫生毒理学];

摘要：

In this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3H)-3-(N-3'-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO(2)) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF(4)) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO(2). QPhNO(2) caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-L-cysteine partially abolished the observed effects related to the QPhNO(2) treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. These findings point to the potential use of the combination of pharmacology and electrochemistry in medicinal chemistry. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：585 / 594

页数：10

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