DOI QR코드

DOI QR Code

Design, Synthesis and in-vitro Screening of New 1H-Pyrazole and 1,2-Isoxazole Derivatives as Potential Inhibitors for ROS and MAPK14 Kinases

  • Al-Sanea, Mohammad M. (Department of Biomolecular Science, University of Science and Technology) ;
  • El-Deeb, Ibrahim M. (Institute for Glycomics, Griffith University, Gold Coast Campus, QLD) ;
  • Lee, So Ha (Chemical Kinomics Research Center, Korea Institute of Science and Technology)
  • Received : 2012.08.08
  • Accepted : 2012.11.14
  • Published : 2013.02.20

Abstract

A new series of 4-(2-(substituted)pyridin-4-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazoles (4a-f) and their 1,2-isoxazole analogues (5a-f) has been rationally designed, synthesized and screened against both ROS and MAPK14 kinases. Compounds 4b, 4c and 4e showed moderate inhibitions against both ROS and MAPK14 kinases. Compound 4e has showed the strongest inhibitions with IC50 values of 1.25 ${\mu}M$ and 3.00 ${\mu}M$ against ROS and MAPK14 kinases, respectively. A brief structure-activity relationship study and a molecular modeling study were made revealing a group of essential structural features for good kinase inhibitory activity within this new class of kinase inhibitors.

Keywords

References

  1. Uitdehaag, J. C.; Verkaar, F.; Alwan, H.; de Man, J.; Buijsman, R. C.; Zaman, G. J. Br. J. Pharmacol. 2012, 166, 858. https://doi.org/10.1111/j.1476-5381.2012.01859.x
  2. El-Deeb, I. M.; Yoo, K. H.; Lee, S. H. Med. Res. Rev. 2011, 31, 794.
  3. Birchmeier, C.; Sharma, S.; Wigler, M. Proc. Natl. Acad. Sci. USA 1987, 84, 9270. https://doi.org/10.1073/pnas.84.24.9270
  4. Rikova, K.; Guo, A.; Zeng, Q.; Possemato, A.; Yu, J.; Haack, H.; Nardone, J.; Lee, K.; Reeves, C.; Li, Y.; Hu, Y.; Tan, Z.; Stokes, M.; Sullivan, L.; Mitchell, J.; Wetzel, R.; MacNeill, J.; Ren, J. M.; Yuan, J.; Bakalarski, C. E.; Villen, J.; Kornhauser, J. M.; Smith, B.; Li, D.; Zhou, X.; Gygi, S. P.; Gu, T. L.; Polakiewicz, R. D.; Rush, J.; Comb, M. J. Cell 2007, 131, 1190. https://doi.org/10.1016/j.cell.2007.11.025
  5. Shiffman, D.; Ellis, S. G.; Rowland, C. M.; Malloy, M. J.; Luke, M. M.; Iakoubova, O. A.; Pullinger, C. R.; Cassano, J.; Aouizerat, B. E.; Fenwick, R. G.; Reitz, R. E.; Catanese, J. J.; Leong, D. U.; Zellner, C.; Sninsky, J. J.; Topol, E. J.; Devlin, J. J.; Kane, J. P. Am. J. Hum. Genet. 2005, 77, 596. https://doi.org/10.1086/491674
  6. Oguri, M.; Kato, K.; Hibino, T.; Yokoi, K.; Segawa, T.; Matsuo, H.; Watanabe, S.; Nozawa, Y.; Murohara, T.; Yamada, Y. Atherosclerosis 2007, 194, 172. https://doi.org/10.1016/j.atherosclerosis.2006.12.019
  7. Yamada, Y.; Kato, K.; Yoshida, T.; Yokoi, K.; Matsuo, H.; Watanabe, S.; Ichihara, S.; Metoki, N.; Yoshida, H.; Satoh, K.; Aoyagi, Y.; Yasunaga, A.; Park, H.; Tanaka, M.; Nozawa, Y. J. Mol. Med. 2008, 21, 83.
  8. Lenassi, M.; Plemenitas, A. Radiol. Oncol. 2006, 40, 51.
  9. Lindstorm, T. M.; Robinson, W. H. Rheum. Dis. Clin. North Am. 2010, 36, 367. https://doi.org/10.1016/j.rdc.2010.02.005
  10. Genovese, M. C. Arthritis Rheum. 2009, 60, 317. https://doi.org/10.1002/art.24264
  11. Park, B. S.; El-Deeb, I. M.; Yoo, K. H.; Oh, C. H.; Cho, S. J.; Han, D. K.; Lee, H. S.; Lee, J. Y.; Lee, S. H. Bioorg. Med. Chem. Lett. 2009, 19, 4720. https://doi.org/10.1016/j.bmcl.2009.06.066
  12. El-Deeb, I. M.; Park, B. S.; Jung, S. J.; Yoo, K. H.; Oh, C. H.; Cho, S. J.; Han, D. K.; Lee, J. Y.; Lee, S. H. Bioorg. Med. Chem. Lett. 2009, 19, 5622. https://doi.org/10.1016/j.bmcl.2009.08.029
  13. Anastassiadis, T.; Deacon, S. W.; Devarajan, K.; Ma, H.; Peterson, J. R. Nat. Biotechnol. 2011, 29, 1039. https://doi.org/10.1038/nbt.2017
  14. Reaction Biology Corporation Web Site, www.reactionbiology. com.www.rcsb.org/pdb.

Cited by

  1. ChemInform Abstract: Design, Synthesis and in vitro Screening of New 1H-Pyrazole and 1,2-Isoxazole Derivatives as Potential Inhibitors for ROS and MAPK14 Kinases. vol.44, pp.40, 2013, https://doi.org/10.1002/chin.201340122
  2. Synthesis and in Vitro Screening of Phenylbipyridinylpyrazole Derivatives as Potential Antiproliferative Agents vol.20, pp.1, 2015, https://doi.org/10.3390/molecules20011031
  3. ]pyrimidine Derivatives as Potential Antiproliferative Agents vol.36, pp.7, 2015, https://doi.org/10.1002/bkcs.10363
  4. Recent advances in isoxazole chemistry vol.84, pp.4, 2015, https://doi.org/10.1070/RCR4503
  5. Theoretical studies on proton transfer reaction of 3(5)-substituted pyrazoles vol.126, pp.1, 2013, https://doi.org/10.1007/s12039-013-0569-5
  6. Synthesis and in vitro evaluation of substituted tetrahydroquinoline-isoxazole hybrids as anticancer agents vol.28, pp.8, 2013, https://doi.org/10.1007/s00044-019-02363-z
  7. Synthesis and biological evaluation of small molecule modulators of CDK8/Cyclin C complex with phenylaminoquinoline scaffold vol.8, pp.None, 2013, https://doi.org/10.7717/peerj.8649