Synthesis, Characterization and Antimicrobial Activity of Novel Pharmacophores Incorporating Imidazoline-Oxazoline Scaffold

  • Barakat, Assem ;
  • Al-Majid, Abdullah Mohammed ;
  • Al-Qahatany, Faisal M. ;
  • Islam, Mohammad Shahidul ;
  • Al-Agamy, Mohamed H.M.
  • Received : 2013.08.30
  • Accepted : 2013.11.29
  • Published : 2014.02.20


In this work, synthesis, characterization and antimicrobial activity of series of imidazolines-oxazolines scaffolds 5a-f and 10a-d have been investigated. All the imidazolines-oxazolines derivatives were prepared from acid derivatives 1 and 6a-c, and enantiomerically pure (S)-2-amino-3-methyl-1-butanol in four steps with excellent optical purity. The structures of all newly synthesized compounds have been elucidated by $^1H$, $^{13}C$ NMR, GCMS, and IR spectrometry. Their purity was confirmed using elemental analysis. Some newly synthesized compounds were examined to in-vitro antimicrobial activity. Among the prepared products 10d was found to exhibits the most active against all tested bacteria and fungi with minimal inhibitory concentration (MIC) ranged between 21.9 and $42.6{\mu}g/mL$.


Imidazoline;Oxazoline;Antimicrobial activity


  1. Grimmett, M. R. In: Comprehensive Heterocyclic Chemistry; Katrizky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 3, pp 77-120.
  2. Bousquet, P.; Feldman, J.; Schwartz, J. J. Pharmacol. Exp. Ther. 1984, 230, 232-236.
  3. Tsujii, S.; Rinehart, K. L.; Kashman, Y.; Cross, S. S.; Lui, M. S.; Pomponi, S. A.; Diaz, M. C. J. Org. Chem. 1988, 53, 5446-5453.
  4. Bellina, F.; Cauteruccio, S.; Monti, S.M.; Rossi, R. Bioorg. Med. Chem. Lett. 2006, 16, 5757-5762.
  5. (a) Vassilev, L. T.; Vu, B. T.; Graves, B.; Carvajal, D.; Podlaski, F.; Filipovic, Z.; Kong, N.; Kammlott, U.; Lukacs, C.; Klein, C.; Fotouhi, N.; Liu, E. A. Science 2004, 303, 8.
  6. (b) Merriman, G. H.; Ma, L.; Shum, P.; McGarry, D.; Volz, F.; Sabol, J. S.; Gross, A.; Zhao, Z.; Rampe, D.; Wang, L.; Wirtz-Brugger, F.; Harris, B. A.; Mayer, G.; Taberner, P. V. Eur. J. Pharmacol. 2002, 454, 95-102.
  7. (c) Heinelt, U.; Lang, H.-J.; Hofmeister, A.; Wirth, K. PCT Int. Appl. 2003, WO2003053434.
  8. Dardonville, C.; Rozas, I. Med. Res. Rev. 2004, 24, 639-661.
  9. (a) Dardonville, C.; Rozas, I. Med. Res. Rev. 2004, 24, 639.
  10. (b) Tsujii, S.; Rinehart, K. L.; Kashman, Y.; Cross, S. S.; Lui, M. S.; Pomponi, S. A.; Diaz, M. C. J. Org. Chem. 1988, 53, 5446.
  11. Pagano, G.; Lombardi, A.; Ferraris, M. G.; Imbimbo, B.; Carvallo, P. P. Eur. J. Clin. Pharmacol. 1982, 22, 46947.
  12. Ghosh, A. K.; Mathivanan, P.; Cappiello, J. Tetrahedron: Asymmetry 1998, 9, 1-45.
  13. Gomez, M. G.; Muller, G.; Rocamora, M. Coord. Chem. Rev. 1999, 193-195, 769-835.
  14. McManus, H. A.; Guiry, P. J. Chem. Rev. 2004, 104, 4151-4202.
  15. Zhou, J.; Tang, Y. Chem. Soc. Rev. 2005, 34, 664-676.
  16. Desimoni, G.; Faita, G.; Jorgensen, K. A. Chem. Rev. 2006, 106, 3561-3651.
  17. Hao, X.-Q.; Xu, Y.-X.; Yang, M.-J.; Wang, L.; Niu, J.-L.; Gong, J.-F.; Song, M.-P. Organometallics 2012, 31, 835-846.
  18. Akbas, E.; Berber, I. Eur. J. Med. Chem. 2005, 40, 401-405.
  19. (a) Barakat, A.; Al Majid, A. M. A.; Islam, M. S.; Al-Othman, Z. A. Tetrahedron 2013, 69, 5185-5192.
  20. (b) Islam, M. S.; Al Majid, A. M. A.; Al-Othman, Z. A; Barakat, A. Tetrahedron: Asymmetry 2014, 25, 245-251.
  21. Burke, A. J.; Carreiro, E. P.; Chercheja, S.; Moura, N. M. M.; Ramalho, J. P.; Rorigues, A. I.; Santos, C. I. M. J. Organomet. Chem. 2007, 692, 4863-4874.
  22. Carreiro, E. P.; Chercheja, S.; Burke, A. J.; Ramalho, J. P.; Rodrigues, A. P. J. Mol. Catal. A Chem. 2005, 236, 38-45.
  23. Carreiro, E. P.; Chercheja, S.; Moura, N.; Gertrudes, S. C.; Burke, A. J. Inorg. Chem. Commun. 2006, 9, 823-826.
  24. Barakat, A.; Al-Majid, A. M.; Mabkhot, Y. N.; Yousuf, S. S.; Choudhary, M. I. Acta Cryst. 2013, E69, o919.
  25. Perez, C.; Pauli, M.; Bazevque, P. Acta Biol. Med. Exp. 1990, 15, 113.
  26. Scott, A. C. In: Laboratory Control of Antimicrobial Therapy, 13th ed.; Collee, J. G., Duguid, J. P., Fraser, A. G., Marmion, B. P., Eds.; Mackie and MacCartney Practical Medical Microbiology: 2 Churchill Livingstone, 1989; pp 161-181.
  27. Nickerson, D. M.; Mattson, A. E. Chem. Eur. J. 2012, 18, 8310-8314.