Journal of Chemical Crystallography

, Volume 42, Issue 8, pp 783–789 | Cite as

Synthesis, Antimicrobial and Cholinesterase Enzymes Inhibitory Activities of Indeno Imidazoles and X-Ray Crystal Structure of 3a,8a-Dihydroxy-1,3-diphenyl-1,3,3a,8a-tetrahydro-indeno[1,2-d]imidazole-2,8-dione

  • Raza Murad Ghalib
  • Rokiah Hashim
  • Solhe F. Alshahateet
  • Sayed Hasan Mehdi
  • Othman Sulaiman
  • Kit-Lam Chan
  • Vikneswaran Murugaiyah
  • Ali Jawad
Original Paper


Two indeno imidazoles have been synthesized by the reaction of ninhydrin with diphenylurea and diphenylthiourea. The structures have been determined by spectral analysis. The supramolecular behavior of 3a,8a-Dihydroxy-1,3-diphenyl-1,3,3a,8a-tetrahydro-indeno[1,2-d]imidazole-2,8-dione (1) was thoroughly analyzed and reported using X-ray single crystal technique and concepts. The presence of oxygen and nitrogen atoms led to very interesting supramolecular motifs interactions such as nitrogen–oxygen, nitrogen–nitrogen, oxygen–oxygen, nitrogen–hydrogen, and oxygen–hydrogen. 3a,8a-dihydroxy-1,3-diphenyl-2-thioxo-2,3,3a,8a-tetrahydro-1H-indeno[1,2-d]imidazol-8-one 2 showed good antibacterial activity against B. subtilis and P. aeruginosa, while 3a,8a-dihydroxy-1,3-diphenyl-1,3,3a,8a-tetrahydro-indeno[1,2-d]imidazole-2,8-dione 1 only showed antibacterial activity against P. aeruginosa. Both of 1 and 2 were inactive against C. albicans. Derivative 2 demonstrated good cholinesterase enzyme activity unlike derivative 1 which has weak inhibitory activity against these enzymes. Furthermore, 2 was found to be a selective butyrylcholinesterase enzyme inhibitor that has potential use for prevention of further neurodegeneration as well for symptomatic treatment of Alzheimer patients.

Graphical Abstract

The non-covalent interactions involved in the crystal structure of 3a,8a-Dihydroxy-1,3-diphenyl-1,3,3a,8a-tetrahydro-indeno[1,2-d]imidazole-2,8-dione (1) were investigated and reported in terms of crystal engineering and supramolecular chemistry. Different motifs of N···H and O···H interactions as well as N···O, N···N, and O···O are adopted by the crystal structure and led to a strong crystal packing.


Synthesis Crystal structure 3a,8a-Dihydroxy-1,3-diphenyl-1,3,3a,8a-tetrahydro-indeno[1,2-d]imidazole-2,8-dione 3a,8a-Dihydroxy-1,3-diphenyl-2-thioxo-2,3,3a,8a-tetrahydro-1H-indeno[1,2-d]imidazol-8-one Antimicrobial activity Cholinesterase enzymes inhibitory activity 



We would like to acknowledge Universiti Sains Malaysia (USM) for the Postdoctoral Fellowship to Dr. Raza Murad Ghalib. We would also like to thank Ms Liew Wai Lam, Ms Claira Arul Aruldass and Mr Mani Maran Marimuthu for their contribution in the present study.


  1. 1.
    Hasenknopf B, Lehn J-M, Kneisel BO, Baum G, Fenske D (1996) Angew Chem Int Ed 35:1838CrossRefGoogle Scholar
  2. 2.
    Day AI (2002) Angew Chem Int Ed 41:275CrossRefGoogle Scholar
  3. 3.
    Bravo JA (1998) Eur J Org Chem 1998:2565CrossRefGoogle Scholar
  4. 4.
    Anderson S, Anderson HL, Bashall A, McPartlin M, Sanders JKM (1995) Angew Chem Int Ed 34:1096CrossRefGoogle Scholar
  5. 5.
    Freeman WA (1984) Acta Crystallogr B 40:382CrossRefGoogle Scholar
  6. 6.
    Schmitt J-L, Stadler A-M, Kyritsakas N, Lehn J-M (2003) Helv Chim Acta 86:1598CrossRefGoogle Scholar
  7. 7.
    Lehn JM (1993) Science 260(5115):1762CrossRefGoogle Scholar
  8. 8.
    Lehn J-M (1995) Supramolecular chemistry. Wiley-VCH. ISBN 978-3527293117Google Scholar
  9. 9.
    Oshovsky GV, Reinhoudt DN, Verboom W (2007) Angew Chem Int Ed 46(14):2366CrossRefGoogle Scholar
  10. 10.
    Alshahateet SF, Bishop R, Craig DC, Scudder ML (2011) Cryst Growth Des 11:4474–4483CrossRefGoogle Scholar
  11. 11.
    Alshahateet SF, Rahman ANMM, Bishop R, Craig DC, Scudder ML (2002) CrystEngComm 4(97):585–590CrossRefGoogle Scholar
  12. 12.
    MacNicol DD, Downing GR (1996) In: MacNicol D, Toda F, Bishop R (eds) Comprehensive supramolecular chemistry, vol. 6 solid-state supramolecular chemistry: crystal engineering. Pergamon Press, Oxford, Ch 14, pp 421–464Google Scholar
  13. 13.
    Alshahateet SF, Bishop R, Craig DC, Scudder ML (2001) CrystEngComm 3(48):225–229CrossRefGoogle Scholar
  14. 14.
    Alshahateet SF, Bishop R, Craig DC, Scudder ML (2004) Cryst Growth Des 4:837–844CrossRefGoogle Scholar
  15. 15.
    Kooli F, Hian PC, Weirong Q, Alshahateet SF, Chen F (2006) J Porous Mater 13:319–324CrossRefGoogle Scholar
  16. 16.
    Alshahateet SF, Bishop R, Craig DC, Scudder ML (2003) CrystEngComm 3:417–421CrossRefGoogle Scholar
  17. 17.
    Alshahateet SF, Bishop R, Craig DC, Scudder ML (2010) Cryst Growth Des 10:1842–1847CrossRefGoogle Scholar
  18. 18.
    Alshahateet SF, Bishop R, Scudder ML, Hu CY, Lau EHE, Kooli F, Judeh ZMA, Chow PS, Tan RBH (2005) CrystEngComm 7:139–142CrossRefGoogle Scholar
  19. 19.
    Alshahateet SF, Bishop R, Craig DC, Scudder ML (2001) CrystEngComm 3(55):264–269CrossRefGoogle Scholar
  20. 20.
    Alshahateet SF, Bishop R, Craig DC, Kooli F, Scudder ML (2008) CrystEngComm 10:297–305CrossRefGoogle Scholar
  21. 21.
    Alshahateet SF, Ong TT, Bishop R, Kooli F, Messali M (2006) Cryst Growth Des 6(7):1676–1683CrossRefGoogle Scholar
  22. 22.
    Alshahateet SF, Bishop R, Craig DC, Scudder ML, Ung AT (2001) Struct Chem 12:251–257CrossRefGoogle Scholar
  23. 23.
    Eloff JN (1998) Planta Med 64:711–713CrossRefGoogle Scholar
  24. 24.
    Ahmed T, Gilani AH (2009) Pharmacol Biochem Behav 91:554–559CrossRefGoogle Scholar
  25. 25.
    Siemens Energy and Automation, Inc (1996) SMART and SAINT software reference manuals, Version 4.0. Analytical Instrumentation, Madison, WIGoogle Scholar
  26. 26.
    Sheldrick GM (1996) SADABS. University of Göttingen, GöttingenGoogle Scholar
  27. 27.
    Sheldrick GM (2008) Acta Crystallogr A64:112–122Google Scholar
  28. 28.
    Weinstock M, Groner E (2008) Chem-Biol Interact 175:216–221CrossRefGoogle Scholar
  29. 29.
    Mesulam M, Guillozet A, Shaw P, Quinn B (2002) Neurobiol Dis 9:88–93CrossRefGoogle Scholar
  30. 30.
    Desiraju GR, Steiner T (1999) The weak hydrogen bond in structural chemistry and biology. Oxford Science Publications, OxfordGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Raza Murad Ghalib
    • 1
  • Rokiah Hashim
    • 1
  • Solhe F. Alshahateet
    • 2
  • Sayed Hasan Mehdi
    • 1
  • Othman Sulaiman
    • 1
  • Kit-Lam Chan
    • 3
  • Vikneswaran Murugaiyah
    • 4
  • Ali Jawad
    • 5
  1. 1.School of Industrial TechnologyUniversiti Sains MalaysiaPulau-PinangMalaysia
  2. 2.Department of ChemistryMutah UniversityAl KarakJordan
  3. 3.Discipline of Pharmaceutical Chemistry, School of Pharmaceutical SciencesUniversiti Sains MalaysiaPenangMalaysia
  4. 4.Discipline of Pharmacology, School of Pharmaceutical SciencesUniversiti Sains MalaysiaPenangMalaysia
  5. 5.Department of Applied PhysicsZakir Husain College of Engineering and Technology, AMUAligarhIndia

Personalised recommendations