Structure-Activity Relationship of Chroman-2-carboxylic Acid N-Arylalkylamide Derivatives

크로만-2-카르복실산 N-아릴알킬아마이드 유도체의 구조-활성관계

  • Received : 2013.11.05
  • Accepted : 2013.11.26
  • Published : 2013.12.31

Abstract

In our previous studies, 6-hydroxy-7-methoxychroman-2-carboxylic acid N-phenylamide (KL-1156) was identified as a good inhibitor of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activation. In continuation of our study, we describe the structure-activity relationship of chroman derivatives containing N-arylalkyl groups and their NF-${\kappa}B$ inhibitory activities. In addition, inhibitory effects of cell proliferation are evaluated against human cancer cell lines (NCI-H23 and PC-3). The most active compounds 3i and 3j contained diphenylethyl and diphenylpropyl side chain on amide nitrogen.

Keywords

References

  1. Beg, A. A. and Baltimore, D. : An essential role for NF-$\kappa$B in preventing TNF-$\alpha$-induced cell death. Science 274, 782 (1996). https://doi.org/10.1126/science.274.5288.782
  2. Alcamo, E., Mizqerd, J. P., Horwitz, B. H., Bronson, R., Beq, A. A., Scoot, M., Doerschuk, C. M., Hynes, R. O. and Baltimore, D. : Targeted mutation of TNF receptor I rescues the RelA-deficient mouse and reveals a critical role for NF-${\kappa}B$ in leukocyte recruiment. J. Immunol. 167, 1592 (2001). https://doi.org/10.4049/jimmunol.167.3.1592
  3. Kumar, A., Takada, Y., Boriek, A. M. and Aggarwal, B. B. : Nuclear factor-$\kappa$B: its role in health and disease. J. Mol. Med. 82, 434 (2004).
  4. Kim, B. H., Reddy, A. M., Lee, K. H., Chung, E. Y., Cho, S. M., Lee, H., Min, K. R. and Kim, Y. : Inhibitory mechanism of chroman compound on LPS-induced nitric oxide production and nuclear factor-kappaB activation. Biochem. Biophys. Res. Commun. 325, 223 (2004). https://doi.org/10.1016/j.bbrc.2004.10.026
  5. Kwak, J. H., Won, S. W., Kim, T. J., Roh, E., Kang, H. Y., Lee, H. W., Jung, J. K., Hwang, B. Y., Kim, Y., Cho, J. and Lee, H. : Synthesis of chroman-2-carboxylic acid N-(substituted) phenylamides and their inhibitory effect on nuclear factor-$\kappa$B (NF-$\kappa$B) activation. Arch. Pharm. Res. 31, 133 (2008). https://doi.org/10.1007/s12272-001-1131-4
  6. Yi, W., Han, S. B., Kim, Y., Jung, J. K. and Lee, H. : Synthesis and inhibitory activity on NF-$\kappa$B activation of chroman-2- carboxylic acid N-heteroarylamide derivatives. Yakhak Hoeji 56, 186 (2012).
  7. Skehan, P., Storeng, R., Scudiero, D. A., Monks, A., McMahon, J., Vistica, D., Warren, J. T., Bokesch, H., Kenney, S. and Boyd, M. R. : New colorimetric cytotoxicity assay for anticancer-drug screening. J. Natl. Cancer Inst. 82, 1107 (1990). https://doi.org/10.1093/jnci/82.13.1107