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Acta Biologica Hungarica

, Volume 64, Issue 2, pp 249–261 | Cite as

Synthesis and Different Biological Activities of Novel Benzoxazoles

  • O. Temiz-ArpaciEmail author
  • B. Eylem Cifcioglu Goztepe
  • Fatma Kaynak-Onurdag
  • Selda Ozgen
  • Fatma Sezer Senol
  • I. Erdogan Orhan
Article

Abstract

A series of 2-[4-(4-substitutedbenzamido/phenylacetamido/butanamido)phenyl]-5-ethylsulphonyl-benzoxazole derivatives were synthesized and biologically evaluated as possible antimicrobial agents and inhibitors of tyrosinase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). The results demonstrated that the synthesized compounds exhibited a broad spectrum of activity with minimum inhibitory concentration (MIC) values of 128-16 µg/ml against some Gram-positive, Gram-negative bacteria as well as Candida albicans and C. krusei. The compound 10 displayed higher activity in this series against methicilline resistant Staphylococcus aureus (MRSA) with a MIC value of 16 µg/ml than the compared control drugs ampicillin and ceftriaxone. Compound 14 showed moderate tyrosinase inhibition, however, none of the compounds showed effect as inhibitor of AChE and BChE.

Keywords

Benzoxazoles antibacterial activity antifungal activity enzyme inhibition synthesis 

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References

  1. 1.
    Andriole, V. T. (1999) Current and future antifungal therapy: new targets for antifungal agents. J. Antimicrob. Chemother. 44, 151–162.CrossRefGoogle Scholar
  2. 2.
    Akbay, A., Oren, I., Temiz-Arpaci, O., Aki-Sener, E., Yalçin, I. (2003) Synthesis and HIV-1 Reverse Transcriptase Inhibitor activity of some 2,5,6-substituted benzoxazole, benzimidazole, benzothiazole and oxazolo(4,5-b)pyridine derivatives. Arzneim. Forsch. 54, 266–271.Google Scholar
  3. 3.
    Aki-Sener, E., Temiz-arpaci, O., Yalçin, I., Altanlar, N. (2000) Synthesis and microbiological activity of some 5-benzamido- and 5-phenylacetamido-substituted 2-phenylbenzoxazole derivatives. Il Farmaco 55, 397–405.CrossRefGoogle Scholar
  4. 4.
    Alanso, D., Dorronsoro, I., Rubio, L., Munoz, E., Garcia-Palomero, E., Delmonte, M. (2005) Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE. Bioorg. Med. Chem. 13, 6588.CrossRefGoogle Scholar
  5. 5.
    Cacebelos, R., Alvarez, A., Fernandez-Novoa, L., Lomardi, V. R. (2000) A pharmacogenomic approach to Alzheimer’s disease. Acta Neurol. Scand. 176, 12–19.CrossRefGoogle Scholar
  6. 6.
    Brown, R. N., Cameron, R., Chalmers, D. K., Hamilton, S., Luttick, A., Krippner, G. Y., McConnell, D. B., Nearn, R., Stanislawski, P. C., Tucker, S. P., Watson, K. G. (2005) 2-Ethoxybenzoxazole as a bioisosteric replacement of an ethyl benzoate group in a human rhinovirus (HRV ) capsid binder. Bioorg. Med. Chem. Letters 15, 2051–2055.CrossRefGoogle Scholar
  7. 7.
    CLSI (formerly NCCLS) (2006) ReferencesMethod for Broth Dilution Antifungal Susceptibility Testing Yeast, Approved Standard, M27-A3. Clinical and Laboratory Standards Institute, Wayne, PA, USA.Google Scholar
  8. 8.
    CLSI (formerly NCCLS) (2008) Performance Standards for Antimicrobial Susceptibility Testing; 16th Informational Supplement, CLSI M100-S18. Clinical and Laboratory Standards Institute, Wayne, PA, USA.Google Scholar
  9. 9.
    Elman, G. L., Courtney, K. D., Andres, V., Featherstone, R. M. (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7, 88–95.CrossRefGoogle Scholar
  10. 10.
    Haansuu, J. P., Klika, K. D., Söderholm, P. P., Ochaveranko, V. V., Pihlaja, K., Haahtela, K. K., Vuorela, P. M. (2001) Isolation and biological activity of frankiamide. J. Ind. Microbiol. Biotechnol. 27, 62–66.CrossRefGoogle Scholar
  11. 11.
    Huang, S. T., Hsei, I. J., Chen, C. (2006) Synthesis and anticancer evaluation of bis(benzimidazoles), bis(benzoxazoles), and benzothiazoles. Bioorg. Med. Chem. 14, 6106–6119.CrossRefGoogle Scholar
  12. 12.
    Khan, M. T. H. (2007) Molecular design of tyrosinase inhibitors: A critical review of promising novel inhibitors from synthetic origins. Pure Appl. Chem. 79, 2277–2295.CrossRefGoogle Scholar
  13. 13.
    Kumar, D., Jacob, M. R., Reynolds, M. B., Kerwin, S. M. (2002) Synthesis and evaluation of anticancer benzoxazoles and benzimidazoles related to UK-1. Bioorg. Med. Chem. 10, 3997–4004.CrossRefGoogle Scholar
  14. 14.
    Jia, P., Sheng, R., Zhang, J., Fang, L., He, Q., Yang, B. (2009) Design, synthesis and evaluation of galanthamine derivatives as acetylcholinesterase inhibitors. Eur. J. Med. Chem. 44, 772–784.CrossRefGoogle Scholar
  15. 15.
    Marcelo, F., Silva, F. V. M., Goulart, M., Justino, J., Sinay, P., Bleriot, Y. (2009) Synthesis of novel purine nucleosides towards a selective inhibition of human butyrylcholinesterase. Bioorg. Med. Chem. 17, 5106.CrossRefGoogle Scholar
  16. 16.
    Díez-Martin, D., Kotecha, N. R., Ley, S. V., Mantegani, S., Menéndez, J. C., Organ, H. M., White, A. D. (1992) Total synthesis of the ionophore antibiotic CP-61,405 (routiennocin). Tetrahedron 48, 7899–7938.CrossRefGoogle Scholar
  17. 17.
    Masuda, T., Yamashita, D., Takeda, Y., Yonemori, S. (2005) Screening for tyrosinase inhibitors among extracts of seashore plants and identification of potent inhibitors from Garcinia subelliptica. Biosci. Biotechnol. Biochem. 69, 197–201.CrossRefGoogle Scholar
  18. 18.
    McKee, M. L., Kerwin, S. M. (2008) Synthesis, metal ion binding, and biological evaluation of new anticancer 2-(2’-hydroxyphenyl) benzoxazole analogs of UK-1. Bioorg. Med. Chem. 16, 1775–1783.CrossRefGoogle Scholar
  19. 19.
    Moustafa, M. A., Gineinah, M. M., Nasr, M. N., Bayoumi, W. A. (2004) Novel analogues of sydnone: synthesis, characterization and antibacterial evaluation. Arch. Pharm. (Weinheim) 337, 427–433.CrossRefGoogle Scholar
  20. 20.
    Murty, M. S. R., Ram, K. R., Rao, R. W., Yadav, J. S., Rao, J. V., Cheriyan, V. T., Anto, R. J. (2011) 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. 20, 576–586.CrossRefGoogle Scholar
  21. 21.
    Oksuzoglu, E., Tekiner-Gulbas, B., Alper, S., Temiz-Arpaci, O., Ertan, T., Yildiz, I., Diril, N., Sener- Aki, E., Yalcin, I. (2008) Some benzoxazoles and benzimidazoles as DNA topoisomerases I and II inhibitors. J. Enzyme Inhib. Med. Chem. 23, 37–42.CrossRefGoogle Scholar
  22. 22.
    Orhan, I., Aslan, S., Kartal, M., Sener, B., Baser, K. H. C. (2008) Inhibitory effect of Turkish Rosmarinus officinalis L. on acetylcholinesterase and butyrylcholinesterase enzymes. Food Chem. 108, 663–668.CrossRefGoogle Scholar
  23. 23.
    Pinar, A., Yurdakul, P., Yildiz, I., Temiz-Arpaci, O., Acan, N. L., Aki-Sener, E., Yalcin, I. (2004) Some fused heterocyclic compounds as eukaryotic topoisomerase II inhibitors. Biochem. Biophys. Res. Commun. 317, 670.CrossRefGoogle Scholar
  24. 24.
    Prudhomme, M., Guyot, J., Jeminet, G. (1986) Semi-synthesis of A23187 (calcimycin) analogs. IV. Cation carrier properties in mitochondria of analogs with modified benzoxazole rings. Antimicrobial activity. J. Antibiot. 39, 934–937.CrossRefGoogle Scholar
  25. 25.
    Rida, S. M., Ashour, F. A., El-Hawash, S. A. M., ElSemary, M. M., Badr, M. H., Shalaby, M. A. (2005) Synthesis of some novel benzoxazole derivatives as anticancer, anti-HIV-1 and antimicrobial agents. Eur. J. Med. Chem. 40, 949–959.CrossRefGoogle Scholar
  26. 26.
    Sarma, H. K., Sharma, B. K., Tiwari, S. C. (2003) A novel calcimycin antibiotic from Gram-positive actinomycete Frankia microsymbiont. Curr. Sci. 85, 1401–1403.Google Scholar
  27. 27.
    Scarpini, E., Scheltens, P., Feldman, H. (2003) Treatment of Alzheimer’s disease: current status and new perspectives. Lancet Neurol. 2, 539–547.CrossRefGoogle Scholar
  28. 28.
    Temiz-Arpaci, O., Aki-Sener, E., Yalçin, I., Altanlar, N. (2002) Synthesis and antimicrobial activity of some 2-[p-substituted-phenyl]benzoxazol-5-yl-arylcarboxyamides. Arch. Pharm. (Weinheim) 335, 283–288.CrossRefGoogle Scholar
  29. 29.
    Temiz-Arpaci, O., Coban, T., Tekiner-Gulbas, B., Can-Eke, B., Yildiz, I., Aki-Sener, E., Yalçin, I., Iscan, M. (2006) A study on the antioxidant activities of some new benzazole derivatives. Acta Biol. Hung. 57, 201–209.CrossRefGoogle Scholar
  30. 30.
    Temiz-Arpaci, O., Yildiz, I., Ozkan, S., Kaynak, F., Aki-Sener, E., Yalçin, I. (2008) Synthesis and biological activity of some new benzoxazoles. Eur. J. Med. Chem. 43, 1423–1431.CrossRefGoogle Scholar
  31. 31.
    Varga, A., Aki-Sener, E., Yalcin, I., Temiz-Arpaci, O., Tekiner Gulbas, B., Cherepney, G., Molnar, J. (2005) Induction of apoptosis and necrosis by resistance benzazoles and benzoxazines on tumour cell line mouse lymphoma L5718 Mdr+cells. In Vivo 19, 1087–1091.PubMedGoogle Scholar
  32. 32.
    Vinsova, J., Horak, V., Buchta, V., Kaustova, J. (2005) Highly lipophilic benzoxazoles with potential antibacterial activity. J. Molecules 10, 783–793.CrossRefGoogle Scholar
  33. 33.
    Yan, Q., Chao, R., Yi, W., Chen, Z., Wen, H., Ma, L., Song, H. (2009) Inhibitory effects of 5-benzylidene barbiturate derivatives on mushroom tyrosinase and their antibacterial activities. Eur. J. Med. Chem. 44, 4235–4243.CrossRefGoogle Scholar
  34. 34.
    Yi, W., Cao, R., Peng, W., Wen, H., Yan, Q., Zhou, B., Ma, L., Song, H. (2010) Synthesis and biological evaluation of novel 4-hydroxybenzaldehyde derivatives as tyrosinase inhibitors. Eur. J. Med. Chem. 45, 639–646.CrossRefGoogle Scholar

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© Akadémiai Kiadó, Budapest 2013

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  • O. Temiz-Arpaci
    • 1
    Email author
  • B. Eylem Cifcioglu Goztepe
    • 1
  • Fatma Kaynak-Onurdag
    • 2
  • Selda Ozgen
    • 2
  • Fatma Sezer Senol
    • 3
  • I. Erdogan Orhan
    • 3
    • 4
  1. 1.Department of Pharmaceutical Chemistry, Faculty of PharmacyAnkara UniversityTandogan, AnkaraTurkey
  2. 2.Department of Microbiology, Faculty of PharmacyGazi UniversityEtiler, AnkaraTurkey
  3. 3.Department of Pharmacognosy, Faculty of PharmacyGazi UniversityEtiler, AnkaraTurkey
  4. 4.Pharmacognosy Unit, Faculty of PharmacyEastern Mediterranean UniversityGazimagosa, The Northern CyprusTurkey

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