Home Life Sciences Biological evaluation and docking studies of some benzoxazole derivatives as inhibitors of acetylcholinesterase and butyrylcholinesterase
Article
Licensed
Unlicensed Requires Authentication

Biological evaluation and docking studies of some benzoxazole derivatives as inhibitors of acetylcholinesterase and butyrylcholinesterase

  • Ozlem Temiz-Arpaci EMAIL logo , Mustafa Arisoy , Duygu Sac , Fatima Doganc , Meryem Tasci , Fatma Sezer Senol and Ilkay Erdogan Orhan
Published/Copyright: August 9, 2016

Abstract

A series of 2,5-disubstituted-benzoxazole derivatives (1–13) were evaluated as possible inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The results demonstrated that the compounds exhibited a broad spectrum of AChE and BChE inhibitory activity ranging between 6.80% and 90.21% except one compound which showed no activity against AChE at the specified molar concentration. Another derivative displayed a similar activity to that of reference drug (galanthamine) for inhibition of AChE and BChE. In addition, molecular docking of the compounds into active site of AChE was performed using recombinant human AChE (PDB ID: 4ey6) in order to understand ligand–protein interactions.

Acknowledgements

This work was financially supported by Ankara University Research Fund (Grant No. 16H 0237001).

References

1. Scarpini E, Schelterns P, Feldman H. Treatment of Alzheimer’s disease: current status and new perspectives. Lancet Neurol 2003;2:539–47.10.1016/S1474-4422(03)00502-7Search in Google Scholar

2. Shan WJ, Huang L, Zhou Q, Meng FC, Li XS. Synthesis and biological evaluation of 9-N-substituted berberine derivatives as multifunctional agents of antioxidant, inhibitors of acetylcholinesterase, butyrylcholinesterase, amyloid-beta-aggregation. Eur J Med Chem 2011;46:5885–93.10.1016/j.ejmech.2011.09.051Search in Google Scholar

3. Szymanski P, Janik A, Zurek E, Mikiciuk-Olasik E. Design, synthesis and biological evaluation of new 2-benzoxazolinone derivatives as potential cholinesterase inhibitors for therapy of alzheimer’s disease. Pharmazie 2011;66:399–403.10.1002/chin.201134123Search in Google Scholar

4. Cacabelos R, Alvarez A, Fernandez-Novoa L, Lomardi VR. A pharmacogenomic approach to Alzheimer’s disease. Acta Neurol Scand Suppl 2000;176:12–9.10.1034/j.1600-0404.2000.00302.xSearch in Google Scholar

5. Alonso D, Dorronsoro I, Rubio L, Munoz P, Garcia-Palomero E, Del Monte M, et al. Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE. Bioorg Med Chem 2005;13:6588–97.10.1016/j.bmc.2005.09.029Search in Google Scholar

6. Jia P, Sheng R, Zhang J, Fang L, He Q, Yang B, et al. Design, synthesis and evaluation of galanthamine derivatives as acetylcholinesterase inhibitors. Eur J Med Chem 2009;44:772–84.10.1016/j.ejmech.2008.04.018Search in Google Scholar

7. Marcelo F, Silva FV, Goulart M, Justino J, Sinay P, Bleriot Y, et al. Synthesis of novel purine nucleosides towards a selective inhibition of human butyrylcholinesterase. Bioorg Med Chem 2009;17:5106–16.10.1016/j.bmc.2009.05.057Search in Google Scholar

8. Diez-Martin D, Kotecha NR, Ley SV, Mantegani S, Menendes JC, Organ HM, et al. Total synthesis of the ionophore antibiotic CP-61,405 (routiennocin). Tetrahedron 1992;48:7899–938.10.1016/S0040-4020(01)80467-1Search in Google Scholar

9. Prudhomme M, Guyot J, Jeminet G. Semi-synthesis of A23187 (calcimycin) analogs. IV. Cation carrier properties in mitochondria of analogs with modified benzoxazole rings. Antimicrobial activity. J Antibiotics 1986;39:934–7.10.7164/antibiotics.39.934Search in Google Scholar PubMed

10. Sarma HK, Sharma BK, Tiwari SC. A novel calcimycin antibiotic from Gram-positive actinomycete Frankia microsymbiont. Curr Sci 2003;85:1401–3.Search in Google Scholar

11. Haansuu JP, Klika KD, Söderholm PP, Ovcharenko VV, Pihlaja K, Haahtela KK, et al. Isolation and biological activity of frankiamide. J Ind Microbiol Biotechnol 2001;27:62–6.10.1038/sj.jim.7000164Search in Google Scholar PubMed

12. Arisoy M, Temiz-Arpaci O, Kaynak-Onurdag F, Ozgen S. Novel benzoxazoles: synthesis and antibacterial, antifungal, and antitubercular activity against antibiotic-resistant and -sensitive microbes. Z Naturforsch C 2013;68:453–60.10.1515/znc-2013-11-1204Search in Google Scholar

13. Arisoy, M, Temiz-Arpaci O, Kaynak-Onurdag F, Ozgen S. Synthesis and antimicrobial activity of novel benzoxazoles. Z Naturforsch C 2012;67:466–72.10.1515/znc-2012-9-1004Search in Google Scholar PubMed

14. Temiz-Arpaci O, Eylem Cifcioglu Goztepe B, Kaynak-Onurdag F, Ozgen S, Senol FS, Orhan IE. Synthesis and different biological activities of novel benzoxazoles. Acta Biol Hung 2013;64:249–61.10.1556/ABiol.64.2013.2.10Search in Google Scholar PubMed

15. Arisoy M, Temiz-Arpaci O, Kaynak-Onurdag F, Ozgen S. Synthesis and antimicrobial evaluation of 2-(p-Substituted phenyl)-5-[(4-substituted piperazin-1-yl)acetamido]-benzoxazoles. Z Naturforsch C 2014;69:368–74.10.5560/znc.2014-0024Search in Google Scholar PubMed

16. Vinsova J, Horak V, Buchta V, Kaustova J. Highly lipophilic benzoxazoles with potential antibacterial activity. Molecules 2005;10:783–93.10.3390/10070783Search in Google Scholar PubMed PubMed Central

17. Brown RN, Cameron R, Chalmers DK, Hamilton S, Luttick A, Krippner GY, et al. 2-Ethoxybenzoxazole as a bioisosteric replacement of an ethyl benzoate group in a human rhinovirus (HRV) capsid binder. Bioorg Med Chem Lett 2005;15:2051–5.10.1016/j.bmcl.2005.02.054Search in Google Scholar PubMed

18. Rida SM, Ashour FA, El-Hawash SA, ElSemary MM, Badr MH, Shalaby MA. Synthesis of some novel benzoxazole derivatives as anticancer, anti-HIV-1 and antimicrobial agents. Eur J Med Chem 2005;40:949–59.10.1016/j.ejmech.2005.03.023Search in Google Scholar PubMed

19. Oksuzoglu E, Tekiner-Gulbas B, Alper S, Temiz-Arpaci O, Ertan T, Yildiz I, et al. Some benzoxazoles and benzimidazoles as DNA topoisomerase I and II inhibitors. J Enzyme Inhib Med Chem 2008;23:37–42.10.1080/14756360701342516Search in Google Scholar PubMed

20. Pinar A, Yurdakul P, Yildiz I, Temiz-Arpaci O, Acan NL, Aki-Sener E, et al. Some fused heterocyclic compounds as eukaryotic topoisomerase II inhibitors. Biochem Biophys Res Commun 2004;317:670–4.10.1016/j.bbrc.2004.03.093Search in Google Scholar PubMed

21. Huang ST, Hsei IJ, Chen C. Synthesis and anticancer evaluation of bis(benzimidazoles), bis(benzoxazoles), and benzothiazoles. Bioorg Med Chem 2006;14:6106–19.10.1016/j.bmc.2006.05.007Search in Google Scholar PubMed

22. Kumar D, Jacob MR, Reynolds MB, Kerwin SM. Synthesis and evaluation of anticancer benzoxazoles and benzimidazoles related to UK-1. Bioorg Med Chem 2002;10:3997–4004.10.1016/S0968-0896(02)00327-9Search in Google Scholar

23. McKee ML, Kerwin SM. Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2′-hydroxyphenyl) benzoxazole analogs of UK-1. Bioorg Med Chem 2008;16: 1775–83.10.1016/j.bmc.2007.11.019Search in Google Scholar

24. Murty MSR, Ram KR, Rao RV, Yadav JS, Rao JV, Cheriyan VT, et al. Synthesis and preliminary evaluation of 2-substituted-1,3-benzoxazole and 3-[(3-substituted)propyl]-1,3-benzoxazol-2(3H)-one derivatives as potent anticancer agents. Med Chem Res 2011;20:576–86.10.1007/s00044-010-9353-ySearch in Google Scholar

25. Temiz-Arpaci O, Coban T, Tekiner-Gulbas B, Can-Eke B, Yildiz I, Aki-Sener E, et al. A study on the antioxidant activities of some new benzazole derivatives. Acta Biol Hung 2006;57:201–9.10.1556/ABiol.57.2006.2.7Search in Google Scholar

26. Temiz-Arpaci O, Doganc F, Sac D, Sari E, Kaynak-Onurdag F, Okten S. Synthesis and antimicrobial evaluation of some novel sulfonylamido-benzoxazoles. Acta Biol Hung 2016;67:75–84.10.1556/018.67.2016.1.6Search in Google Scholar

27. Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88–95.10.1016/0006-2952(61)90145-9Search in Google Scholar

28. Orhan I, Aslan S, Kartal M, Sener B, Baser KHC. Inhibitory effect of Turkish Rosmarinus officinalis L. on acetylcholinesterase and butyrylcholinesterase enzymes. Food Chem 2008;108:663–8.10.1016/j.foodchem.2007.11.023Search in Google Scholar PubMed

29. Cheung J, Rudolph MJ, Burshteyn F, Cassidy MS, Gary EN, Love J, et al. Structures of human acetylcholinesterase in complex with pharmacologically important ligands. J Med Chem 2012;55:10282–6.10.1021/jm300871xSearch in Google Scholar PubMed

30. Wu G, Robertson DH, Brooks CL, Vieth M. Detailed analyses of grid base molecular docking: A case study of CDOCKER-A CHARMm-based MD docking algorithm. J Comput Chem 2003;24:1549–62.10.1002/jcc.10306Search in Google Scholar PubMed

Received: 2016-3-16
Revised: 2016-6-29
Accepted: 2016-6-29
Published Online: 2016-8-9
Published in Print: 2016-11-1

©2016 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 31.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/znc-2016-0087/html
Scroll to top button