Skip to main content
SpringerLink
Log in

Effect of Low Charge and High Hydrophobicity on Antimicrobial Activity of the Quinazolinone-Peptide Conjugates

  • Published:
Russian Journal of Bioorganic Chemistry Aims and scope Submit manuscript

Abstract

Peptides of relatively low charge and a high number of hydrophobic amino acids were designed. The amino acid sequence of designed peptides was GXGVP, where X equaled to W, Y, F, D, and T with a combination of hydrophobic, charged and polar units. These peptides were linked to quinazolinones to obtain a new class of compounds with synergistic features. The hybrids displayed antimicrobial activity against Gram-positive and Gram-negative bacteria. In particular, Trp, Tyr, and Phe-containing peptides showed greater antimicrobial potency than the reference standards. Alkyl chain length variations in heterocyclic moiety indicated that hybrids with propyl group were more active than butyl derivatives. Improved results were observed for debenzylated versions of the conjugates compared to their benzylated counterparts. Implementation of the hybrid structures of varying charge, hydrophobicity, and alkyl chain length would be a promising approach to obtaining effective antimicrobial agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

QZN (I):

3-(4-oxo-3,4-dihydroquinazolin-2-yl)propanoic acid

QZN (II):

4-(4-oxo-3,4-dihydroquinazolin-2-yl)butanoic acid

EDCI:

1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide

HOBt:

N-hydroxybenzotriazole

NMM:

N-methylmorpholine

Boc:

tert-butyloxycarbonyl

TFA:

trifluoroacetic acid

References

  1. Corbett, E.L., Watt, C.J., Walker, N., Maher, D., Williams, B.G., Raviglione, M.C., and Dye, C., Arch. Intern. Med., 2003, vol. 163, pp. 1009–1021.

    Article  PubMed  Google Scholar 

  2. Mazurek, G.H., Jereb, J., LoBue, P., Iademarco, M.F., Metchock, B., and Vernon, A., MMWR Recomm. Rep., 2005, vol. 54, pp. 49–55.

    PubMed  Google Scholar 

  3. Taylor, Z., Nolan, C.M., and Blumberg, H.M., MMWR Morb. Mortal Wkly. Rep., 2005, vol. 54, pp. 1–81.

    Google Scholar 

  4. Arnusch, C.J., Bonvin, A.M.J.J., Verel, A.M., Jansen, W.T.M., Liskamp, R.M.J., De Kruijff, B., Pieters, R.J., and Breukink, E., Biochemistry, 2008, vol. 47, pp. 12661–12663.

    Article  CAS  PubMed  Google Scholar 

  5. Albada, H.B., Arnusch, C.J., Branderhorst, H.M., Verel, A.M., Janssen, W.T.M., Breukink, E., De Kruijff, B., Pieters, R.J., and Liskamp, R.M.J., Bioorg. Med. Chem. Lett., 2009, vol. 19, pp. 3721–3724.

    Article  Google Scholar 

  6. Griffin, J.H., Linsell, M.S., Nodwell, M.B., Chen, Q., Pace, J.L., Quast, K.L., Krause, K. M., Farringon, L., Wu, T.X., Higgins, D.L., Jenkins, T.E., Christensen, B.G., and Judice, J.K., J. Am. Chem. Soc., 2003, vol. 125, pp. 6517–6531.

    Article  CAS  PubMed  Google Scholar 

  7. El-Sharief, I.M.S., Ammar, Y.A., Zahran, M.A., Ali, A.H., and El-Gaby, M.S.A., Molecules, 2001, vol. 6, pp. 267–278.

    Article  CAS  Google Scholar 

  8. Roopan, S.M., Maiyalagan, T., Khan, T.F., Can. J. Chem. 2008, vol. 86, pp. 1019–1025.

    Article  CAS  Google Scholar 

  9. Murav’eva, K.M., Arkhangel’skaya, N.V., Shchukina, M.N., and Zykova, T.N., Pershin. Khim. Farm. Zh., 1991, vol. 5, pp. 25–27.

    Google Scholar 

  10. Abdel-Hamid, S.G., J. Indian. Chem. Soc., 1979, vol. 74, pp. 613–618.11. Barker, A.J., Eur. Patent 635498, Chem. Abstr., 1995, vol. 122, p. 214099.

    Google Scholar 

  11. Barker, A.J., Eur. Patent 635498, Chem. Abstr., 1995, vol. 122, p. 214099.

    Google Scholar 

  12. Aziza, M.A., Ibrahim, M.K., and El-Helpy, A.G., Al-Azhar J. Pharm. Sci., 1994, vol. 14, pp. 193–201.

    CAS  Google Scholar 

  13. Hamel, E., Lin, C.M., Plowman, J., Wang, H.K., Lee, K.H., and Paull, K.D., Biochem. Pharmacol., 1996, vol. 51, pp. 53–59.

    Article  CAS  PubMed  Google Scholar 

  14. Terashima, K., Shimamura, H., Kawase, A., Tanaka, Y., Tanimura, T., Kamisaki, T., and Ishizuka, Y., Sato, M., Chem. Pharm. Bull., 1995, vol. 43, pp. 2021–2023.

    Article  CAS  PubMed  Google Scholar 

  15. Gursoy, A. and Karali, N., Farmaco, 1995, vol. 50, pp. 857–866.

    CAS  PubMed  Google Scholar 

  16. Baek, D.J., Park, Y.K., Heo, H.L., Lee, M.H., Yang, Z.Y., and Chio, M.H., Bioorg. Med. Chem. Lett., 1998, vol. 8, pp. 3287–3290.

    Article  CAS  PubMed  Google Scholar 

  17. Griffin, R.J., Srinivasan, S., Bowman, K., Calvert, A.H., Curtin, N.J., Neweli, D.R., Pemberton, L.C., and Golding, B.T., J. Med. Chem., 1998, vol. 41, pp. 5247–5256.

    Article  CAS  PubMed  Google Scholar 

  18. Gadek, T.R. and Nicholas, J.B., Biochem. Pharmacol., 2003, vol. 65, pp. 1–8.

    Article  CAS  PubMed  Google Scholar 

  19. Ryota, S., Jeff, M.P., Lawrence, A.M., Karl, J., Arthur, F.M., Paul, A.W., Ishan, K., Eric, V.A., and Jon, D.R., J. Med. Chem., 2013, vol. 56, pp. 320–329.

    Article  Google Scholar 

  20. Suhas, R., Chandrashekar, S., and Gowda, D.C., Eur. J. Med. Chem., 2011, vol. 46, pp. 704–711.

    Article  CAS  PubMed  Google Scholar 

  21. Suresha, G.P., Suhas, R., Wethroe, K., and Gowda, D.C., Eur. J. Med. Chem., 2011, vol. 46, pp. 2530–2540.

    Article  CAS  PubMed  Google Scholar 

  22. Tossi, A., Sandri, L., and Giangaspero A., Peptide Sci., 2000, vol. 55, pp. 4–30.

    Article  CAS  Google Scholar 

  23. Takahashi, D., Shukla, S.K., Prakash, O., and Zhang G., Biochimie, 2010, vol. 92, pp. 1236–1241.

    Article  CAS  PubMed  Google Scholar 

  24. Teixeira, V., Feio, M.J., and Bastos M., Prog. Lipid Res., 2012, vol. 51, pp. 149–177.

    Article  CAS  PubMed  Google Scholar 

  25. Pasupuleti, M., Schmidtchen, A., and Malmsten M., Crit. Rev. Biotechnol., 2012, vol. 32, pp. 143–171.

    Article  CAS  PubMed  Google Scholar 

  26. Dathe, M., Wieprecht, T., Nikolenko, H., Handel, L., Maloy, W.L., MacDonald, D.L., Beyermann, M., and Bienert, M., FEBS Lett., 1997, vol. 403, pp. 208–212.

    Article  CAS  PubMed  Google Scholar 

  27. Schmidtchen, A., Pasupuleti, M., and Malmsten M., Adv. Colloid Interface Sci., 2014, vol. 205, pp. 265–274.

    Article  CAS  PubMed  Google Scholar 

  28. Li, W., Tan, T., Xu, W., Xu, L., Dong, N., Ma, D., and Shan, A., Amino Acids, 2016, vol. 48, pp. 403–417.

    Article  CAS  PubMed  Google Scholar 

  29. Teixeira, V., Feio, M. J., and Bastos, M., Prog. Lipid. Res., 2012, vol. 51, pp. 149–177.

    Article  CAS  PubMed  Google Scholar 

  30. Khandelia, H. and Kaznessis, Y.N., J. Phys. Chem., 2007, vol. BIII, pp. 242–250.

    Article  Google Scholar 

  31. Izumiya, N., Kato, T., Aoyagi, H., Waki, M., and Kondo, M., Synthetic Aspects of Biologically Active Cyclic Peptides—Gramicidin S and Tyrocidines, Tokyo: Kodansha and New York: John Wiley (Halsted), 1979.

    Google Scholar 

  32. Strom, M.B., Haug, B.E., Skar, M.L., Stensen, W., Stilberg, T., and Svendsen, J.S., J. Med. Chem., 2003, vol. 46, pp. 1567–1570.

    Article  CAS  PubMed  Google Scholar 

  33. Tani, A., Lee, S., Oishi, O., Aoyagi, H., and Ohno, M., J. Biochem., 1995, vol. 117, pp. 560–565.

    Article  CAS  PubMed  Google Scholar 

  34. Fournier, J., Bruneau, C., Dixneuf, P.H., and Lécolier, S., J. Org. Chem., 1991, vol. 56, pp. 4456–4458.

    Article  CAS  Google Scholar 

  35. Wohlrab, A., Lamer, R., and VanNieuwenhze, M.S., J. Am. Chem. Soc., 2007, vol. 129, pp. 4175–4177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Mhaske, S.B. and Argade, N.P., J. Org. Chem., 2001, vol. 66, pp. 9038–9040.

    Article  CAS  PubMed  Google Scholar 

  37. Gowda, D.C., Gowda, B.K.K., and Rangappa, K.S., Synth. React. Inorg. Met. Org. Chem., 2001, vol. 31, pp. 1109–1110.

    Article  CAS  Google Scholar 

  38. Prasad, K.U., Iqbal, M.A., and Urry, D.W., Int. J. Pept. Protein. Res., 1985, vol. 25, pp. 408–413.

    Article  CAS  PubMed  Google Scholar 

  39. Perez, C., Paul, M., and Bazerque, P., Acta. Biol. Med. Exp., 1990, vol. 15, pp. 113–115.

    Google Scholar 

  40. Singh, I. and Singh, V.P., Phytomorphology, 2000, vol. 50, pp. 151–157.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysuru, Karnataka, 570006, India

    Kadallipura Puttaswamy Rakesh,  Shivakumar & Dase Channe Gowda

  2. Postgraduate Department of Chemistry, JSS College of Arts, Commerce, and Science, B N Road, Mysuru, Karnataka, 570025, India

    Suhas Ramesh

Authors
  1. Kadallipura Puttaswamy Rakesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Suhas Ramesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shivakumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dase Channe Gowda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dase Channe Gowda.

Additional information

The article is published in the original.

Supplementary materials are available for this article at 10.1134/S1068162018020036 and are accessible for authorized users.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rakesh, K.P., Ramesh, S., Shivakumar et al. Effect of Low Charge and High Hydrophobicity on Antimicrobial Activity of the Quinazolinone-Peptide Conjugates. Russ J Bioorg Chem 44, 158–164 (2018). https://doi.org/10.1134/S1068162018020036

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162018020036

Keywords

Search

Navigation