New Quinoxaline 1,4-Di-N-oxides for Treatment of Tuberculosis

Abstract

Some quinoxaline 1,4-di-N-oxides derivatives with very different substituents in 2, 3, 6 and 7 positions have been synthesized in order to obtain new hypoxia selective agents. Some of these products have been tested as antituberculosis agents and very interesting results have been obtained from the first screening.

QSAR analysis for quinoxaline-2-carboxylate 1,4-di-N-oxides as anti-mycobacterial agents

“…As a result of the anti-tuberculosis research project, our group published several studies in which the synthesis and biological evaluation of a large amount of quinoxaline and quinoxaline 1,4-di-N-oxide derivatives have been described [5][6][7][8][9][10][11][12][13][14][15]. From these studies, several quinoxaline-2-carboxylate 1,4-N-oxide derivatives, with different patterns of substituents at quinoxaline nucleus, were prepared and they showed important antitubercular activity in vitro, 1-43 ( Fig.…”

“…[18] More than thousand available descriptors exist and are reported in the literature, and one has to decide how to select those that characterize the property under consideration in the best possible manner. Although a large number of structure-activity relationships (SARs) were reported previously for analyzing the biological properties displayed by quinoxaline derivatives, none of these included QSAR results [5][6][7][8][9][10][11][12][13][14][15][19][20][21][22]. A main reason of this can be attributed to the fact that in past decades few experimental biological data on quinoxaline compounds were available for building a quantitative model, but nowadays this drawback is continuously being surmounted by different research groups that register new data into the literature.…”

Quinoxaline 1,4-di-N-Oxide and the Potential for Treating Tuberculosis

“…Herein, our group reported interesting results of 2-quinoxalinecarbonitrile derivatives obtained from the first screening; Carta's team did the same with quinoxaline-2-one derivatives [37]. During these past few years, our group studied the influence of the 1,4-di-N-oxide groups in quinoxaline ring on the antimycobacterial activity, confirming their importance to increase the activity [34][35][36].…”

“…The first publications regarding quinoxaline derivatives as anti-Mycobacterium agents date back to the end of the 1990s [34][35][36]. Herein, our group reported interesting results of 2-quinoxalinecarbonitrile derivatives obtained from the first screening; Carta's team did the same with quinoxaline-2-one derivatives [37].…”

Design of novel iron compounds as potential therapeutic agents against tuberculosis

“…Some of these organic derivatives have shown excellent M. tuberculosis growth inhibition values. It has been observed that generally the lack of the two N-oxide groups has lead to the loss of the antimycobacterial activity [11][12][13][14]. On the other hand, the relationship between iron, mycobacteria and tuberculosis is well known.…”