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

نویسندگان

  • Venkatraman Junnotula
  • Anuruddha Rajapakse
  • Leire Arbillaga
  • Adela López de Cerain
  • Beatriz Solano
  • Raquel Villar
  • Antonio Monge
  • Kent S Gates
چکیده

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.

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عنوان ژورنال:
  • Bioorganic & medicinal chemistry

دوره 18 9  شماره 

صفحات  -

تاریخ انتشار 2010