DNA strand cleaving properties and hypoxia-selective cytotoxicity of 7-chloro-2-thienylcarbonyl-3-trifluoromethylquinoxaline 1,4-dioxide |
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| Authors: | Venkatraman Junnotula Anuruddha Rajapakse Leire Arbillaga Adela López de Cerain Beatriz Solano Raquel Villar Antonio Monge Kent S. Gates |
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| Affiliation: | 1. Departments of Chemistry and Biochemistry, University of Missouri-Columbia, Columbia, MO 65211, USA;2. Laboratorio de Toxicología, Centro de Investigación en Farmacobiología, Aplicada (CIFA), University of Navarra, C/Irunlarrea 1, 31080 Pamplona, Spain;3. Unidad de Investigación y Desarrollo de Medicamentos, Centro de Investigación en Farmacobiología Aplicada (CIFA), University of Navarra, c/Irunlarrea 1, 31080 Pamplona, Spain |
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| Abstract: | 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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