Design and synthesis of novel quinone inhibitors targeted to the redox function of apurinic/apyrimidinic endonuclease 1/redox enhancing factor-1 (Ape1/ref-1)
| Autor: | Meihua Luo, Mark R. Kelley, Richard F. Borch, Rodney L. Nyland |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Magnetic Resonance Spectroscopy
Electrophoretic Mobility Shift Assay Redox Article Cell Line Tumor Drug Discovery Benzoquinones DNA-(Apurinic or Apyrimidinic Site) Lyase Humans AP site Enzyme Inhibitors Transcription factor Cell Proliferation chemistry.chemical_classification Ovarian Neoplasms Chemistry Cell growth Benzoquinone DNA-(apurinic or apyrimidinic site) lyase Quinone Enzyme Biochemistry Drug Design Molecular Medicine Methacrylates Female Propionates Oxidation-Reduction Naphthoquinones |
| Zdroj: | Journal of medicinal chemistry. 53(3) |
| ISSN: | 1520-4804 |
| Popis: | The multifunctional enzyme apurinic endonuclease 1/redox enhancing factor 1 (Ape1/ref-1) maintains genetic fidelity through the repair of apurinic sites and regulates transcription through redox-dependent activation of transcription factors. Ape1 can therefore serve as a therapeutic target in either a DNA repair or transcriptional context. Inhibitors of the redox function can be used as either therapeutics or novel tools for separating the two functions for in vitro study. Presently there exist only a few compounds that have been reported to inhibit Ape1 redox activity; here we describe a series of quinones that exhibit micromolar inhibition of the redox function of Ape1. Benzoquinone and naphthoquinone analogues of the Ape1-inhibitor E3330 were designed and synthesized to explore structural effects on redox function and inhibition of cell growth. Most of the naphthoquinones were low micromolar inhibitors of Ape1 redox activity, and the most potent analogues inhibited tumor cell growth with IC(50) values in the 10-20 microM range. |
| Databáze: | OpenAIRE |
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