Synthesis and Different Biological Activities of Novel Benzoxazoles

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.

References

  1. 1.

    Andriole, V. T. (1999) Current and future antifungal therapy: new targets for antifungal agents. J. Antimicrob. Chemother. 44, 151–162.

    CAS  Article  Google 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.

    Article  Google 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.

    Article  Google 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.

    Article  Google 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.

    CAS  Article  Google 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.

    Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  PubMed  Google Scholar 

  32. 32.

    Vinsova, J., Horak, V., Buchta, V., Kaustova, J. (2005) Highly lipophilic benzoxazoles with potential antibacterial activity. J. Molecules 10, 783–793.

    CAS  Article  Google 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.

    CAS  Article  Google 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.

    CAS  Article  Google Scholar 

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Correspondence to O. Temiz-Arpaci.

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Temiz-Arpaci, O., Goztepe, B.E.C., Kaynak-Onurdag, F. et al. Synthesis and Different Biological Activities of Novel Benzoxazoles. BIOLOGIA FUTURA 64, 249–261 (2013). https://doi.org/10.1556/ABiol.64.2013.2.10

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Keywords

  • Benzoxazoles
  • antibacterial activity
  • antifungal activity
  • enzyme inhibition
  • synthesis