Selective activity against Mycobacterium tuberculosis of new quinoxaline 1,4-di-N-oxides

被引：97

作者：

Vicente, Esther ^{[1
]}

Perez-Silanes, Silvia ^{[1
]}

Lima, Lidia M. ^{[2
]}

Ancizu, Saioa ^{[1
]}

Burguete, Asuncion ^{[1
]}

Solano, Beatriz ^{[1
]}

Villar, Raquel ^{[1
]}

Aldana, Ignacio ^{[1
]}

Monge, Antonio ^{[1
]}

机构：

[1] Univ Navarra, CIFA, Unidad Invest & Desarrollo Medicamentos, Pamplona 31080, Spain

[2] Univ Fed Rio de Janeiro, Fac Farm, Lab Avaliacao & Sintese Substancias Bioativas LAS, BR-21944970 Rio De Janeiro, Brazil

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 01期

关键词：

Quinoxaline; N-Oxide; Antimycobacterial; Tuberculosis; QUINOXALINE-2-CARBONITRILE 1,4-DI-N-OXIDE; ANTIMYCOBACTERIAL ACTIVITY; ANTITUBERCULOSIS ACTIVITY; 1,4-DIOXIDE DERIVATIVES; DNA-DAMAGE; AGENTS; ASSAY;

D O I：

10.1016/j.bmc.2008.10.086

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

New series of 3-phenylquinoxaline 1,4-di-N-oxide with selective activity against Mycobacterium tuberculosis have been prepared and evaluated. Thirty-four of the seventy tested compounds showed an MIC value less than 0.2 mu g/mL, a value on the order of the MIC of rifampicin. Furthermore, 45% of the evaluated derivatives showed a good in vitro activity/toxicity ratio. The most active and selective compounds carry a fluorine atom in the quinoxaline 7-position or in the phenyl substituent para-position. In conclusion, the potency, low cytotoxicity and selectivity of these compounds make them valid lead compounds for synthesizing new analogues, particularly compound 7-methyl-3-(4'-fluoro) phenylquinoxaline-2-carbonitrile 1,4-di-N-oxide (MIC <0.2 mu g/mL and SI > 500). (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：385 / 389

页数：5

共 27 条

[1] DNA damage induced by a quinoxaline 1,4-di-N-oxide derivative (hypoxic selective agent) in Caco-2 cells evaluated by the comet assay [J].