Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Synthesis and Biological Evaluation of Novel IM3829 (4-(2-Cyclohexylethoxy)aniline) Derivatives as Potent Radiosensitizers

  • Ahn, Jiyeon (Division of Radiation Cancer Sciences, Korea Institute of Radiological & Medical Sciences) ;
  • Nam, Ky-Youb (Center for Development and Commercialization Anti-Cancer Therapeutics, Asan Medical Center) ;
  • Lee, Sae-Lo-Oom (Division of Radiation Cancer Sciences, Korea Institute of Radiological & Medical Sciences) ;
  • Ryu, Hwani (Division of Radiation Cancer Sciences, Korea Institute of Radiological & Medical Sciences) ;
  • Choi, Hyun Kyung (Department of Medicinal Chemistry, Jungwon University) ;
  • Song, Jie-Young (Division of Radiation Cancer Sciences, Korea Institute of Radiological & Medical Sciences)
  • Received : 2014.09.11
  • Accepted : 2014.10.08
  • Published : 2014.12.20
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Abstract

Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates the expression of over 200 genes of antioxidant and phase II drug-metabolizing enzymes, and is highly expressed in non-small cell lung cancer (NSCLC). Nine derivatives of 4-(2-cyclohexylethoxy)aniline were designed. Our previous study demonstrated that IM3829 increases radiosensitivity of several lung cancer cells in vitro and in vivo. Here, biological effects of IM3829 derivatives (2a-2i) were evaluated. Compound 2g derivative effectively inhibits mRNA and protein expression of Nrf2 and HO-1. In addition, we observed over two fold enhancement in IR-induced cell death, from $2.90{\pm}0.22$ to $6.02{\pm}0.87$, in H1299 cancer cell-line. Among the nine derivatives, compound 2g derivative exhibited the highest enhancement of radiosensitizing effect via inhibition of Nrf2 activity.

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References

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