Quinoxaline 1,4-Dioxide and Phenazine 5,10-Dioxide. Chemistry and Biology

González, Mercedes; Cerecetto, Hugo; Monge, Antonio

doi:10.1007/7081_2007_066

Cited by 25 publications

(12 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We note that we could not distinguish between SO 2 H and 2•SOH. Although unexpected, the cysteine hyperoxidation is consistent with the propensity of quinoxaline N-oxide compounds to undergo successive one-electron reduction to mono-N-oxide or deoxygenated quinoxaline metabolites (reviewed in González, et al, 2007). This reaction is likely facilitated by oxidation of the highly reactive catalytic cysteine thiols.…”

Section: Resultsmentioning

confidence: 63%

Peroxiredoxin-1 from the Human Hookworm Ancylostoma ceylanicum Forms a Stable Oxidized Decamer and Is Covalently Inhibited by Conoidin A

Nguyen

Pool

Wong

et al. 2013

Chemistry & Biology

View full text Add to dashboard Cite

Summary Hookworms are parasitic nematodes that have a devastating impact on global health, particularly in developing countries. We report a biochemical and structural analysis of a peroxiredoxin from the hookworm Ancylostoma ceylanicum, AcePrx-1. Peroxiredoxins provide antioxidant protection and act as signaling molecules and chaperones. AcePrx-1 is expressed in adult hookworms and can be inactivated by 2,3-bis(bromomethyl)quinoxaline-1,4-dioxide (conoidin A). Conoidin A inactivates AcePrx-1 by alkylating or crosslinking the catalytic cysteines, while maintaining the enzyme in the “locally unfolded” conformation. Irreversible oxidation of the resolving cysteine may contribute additional inhibitory activity. A crystal structure of oxidized AcePrx-1 reveals a disulfide-linked decamer. A helix macrodipole near the active site increases the reactivity of the catalytic cysteines to conoidin A. This work demonstrates the promise of conoidin compounds as probes to evaluate peroxiredoxins as drug targets in human parasites.

show abstract

Section: Resultsmentioning

confidence: 63%

Peroxiredoxin-1 from the Human Hookworm Ancylostoma ceylanicum Forms a Stable Oxidized Decamer and Is Covalently Inhibited by Conoidin A

Nguyen

Pool

Wong

et al. 2013

Chemistry & Biology

View full text Add to dashboard Cite

show abstract

“…For example, various 1,2,4-benzotriazines, 34-40 quinoxaline 1,4-di- N -oxides (e.g. 5 ), 41-47 phenazine 5,10-di- N -oxides ( 6 ), 48-51 and imidazo[1,2-a]quinoxaline N -oxides ( 7 ) 52 exhibit hypoxia-selective cytotoxicity in preclinical tests. In some cases, the compounds also have been shown to display hypoxia-selective DNA-damaging properties analogous to tirapazamine.…”

Section: Introductionmentioning

confidence: 99%

DNA strand cleaving properties and hypoxia-selective cytotoxicity of 7-chloro-2-thienylcarbonyl-3-trifluoromethylquinoxaline 1,4-dioxide

Junnotula

Rajapakse

Arbillaga

et al. 2010

Bioorganic & Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

The heterocyclic N-oxide, 3-amino-1,2,4-benzotriazine 1,4-dioxide (tirapazamine, 1), shows promising antitumor activity in preclinical studies, but there is a continuing need to explore new compounds in this general structural category. In the work described here, we examined the properties of 7-chloro-2-thienylcarbonyl-3-trifluoromethylquinoxaline 1,4-dioxide (9h). We find that 9h causes redox-activated, hypoxia-selective DNA cleavage that mirrors the lead compound, tirapazamine, in both mechanism and potency. Furthermore, we find that 9h displays hypoxia-selective cytotoxicity against human cancer cell lines.

show abstract

“…[10][11][12][13] Multiple anti-infective activities are well known for quinoxaline derivatives. [14,15] Our group has vast experience in the synthesis and biological evaluation of multiple quinoxaline 1,4-di-Noxide derivatives, having identified a broad spectrum of anti-infective activities. [16][17][18][19][20][21][22][23][24][25][26] The evaluation of several libraries of compounds led us to find a series with high in vitro activity against T. cruzi.…”

mentioning

confidence: 99%

Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents

Torres

Moreno‐Viguri

Galiano

et al. 2013

European Journal of Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

ABSTRACT. As a continuation of our research and with the aim of obtaining new agents against Chagas disease, an extremely neglected disease which threatens 100 million people, eighteen new quinoxaline 1,4-di-N-oxide derivatives have been synthesized following the Beirut reaction. The synthesis of the new derivatives was optimized through the use of a new and more efficient microwave-assisted organic synthetic method. The new derivatives showed excellent in vitro biological activity against Trypanosoma cruzi. Compound 17, which was substituted with 2 fluoro groups at the 6-and 7-positions of the quinoxaline ring, was the most active and selective in the cytotoxicity assay. The electrochemical study showed that the most active compounds, which were substituted by electron-withdrawing groups, possessed a greater ease of reduction of the N-oxide groups.

show abstract

Quinoxaline 1,4-Dioxide and Phenazine 5,10-Dioxide. Chemistry and Biology

Cited by 25 publications

References 115 publications

Peroxiredoxin-1 from the Human Hookworm Ancylostoma ceylanicum Forms a Stable Oxidized Decamer and Is Covalently Inhibited by Conoidin A

Peroxiredoxin-1 from the Human Hookworm Ancylostoma ceylanicum Forms a Stable Oxidized Decamer and Is Covalently Inhibited by Conoidin A

DNA strand cleaving properties and hypoxia-selective cytotoxicity of 7-chloro-2-thienylcarbonyl-3-trifluoromethylquinoxaline 1,4-dioxide

Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents

Contact Info

Product

Resources

About