Russian Journal of Bioorganic Chemistry

, Volume 44, Issue 2, pp 158–164 | Cite as

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

  • Kadallipura Puttaswamy Rakesh
  • Suhas Ramesh
  • Shivakumar
  • Dase Channe Gowda


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.


pentapeptides quinazolinones hydrophobic antimicrobial conjugation 



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


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










trifluoroacetic acid


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 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.CrossRefPubMedGoogle Scholar
  2. 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.PubMedGoogle Scholar
  3. 3.
    Taylor, Z., Nolan, C.M., and Blumberg, H.M., MMWR Morb. Mortal Wkly. Rep., 2005, vol. 54, pp. 1–81.Google Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 8.
    Roopan, S.M., Maiyalagan, T., Khan, T.F., Can. J. Chem. 2008, vol. 86, pp. 1019–1025.CrossRefGoogle Scholar
  9. 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. 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. 11.
    Barker, A.J., Eur. Patent 635498, Chem. Abstr., 1995, vol. 122, p. 214099.Google Scholar
  12. 12.
    Aziza, M.A., Ibrahim, M.K., and El-Helpy, A.G., Al-Azhar J. Pharm. Sci., 1994, vol. 14, pp. 193–201.Google Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 15.
    Gursoy, A. and Karali, N., Farmaco, 1995, vol. 50, pp. 857–866.PubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.CrossRefPubMedGoogle Scholar
  18. 18.
    Gadek, T.R. and Nicholas, J.B., Biochem. Pharmacol., 2003, vol. 65, pp. 1–8.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefGoogle Scholar
  20. 20.
    Suhas, R., Chandrashekar, S., and Gowda, D.C., Eur. J. Med. Chem., 2011, vol. 46, pp. 704–711.CrossRefPubMedGoogle Scholar
  21. 21.
    Suresha, G.P., Suhas, R., Wethroe, K., and Gowda, D.C., Eur. J. Med. Chem., 2011, vol. 46, pp. 2530–2540.CrossRefPubMedGoogle Scholar
  22. 22.
    Tossi, A., Sandri, L., and Giangaspero A., Peptide Sci., 2000, vol. 55, pp. 4–30.CrossRefGoogle Scholar
  23. 23.
    Takahashi, D., Shukla, S.K., Prakash, O., and Zhang G., Biochimie, 2010, vol. 92, pp. 1236–1241.CrossRefPubMedGoogle Scholar
  24. 24.
    Teixeira, V., Feio, M.J., and Bastos M., Prog. Lipid Res., 2012, vol. 51, pp. 149–177.CrossRefPubMedGoogle Scholar
  25. 25.
    Pasupuleti, M., Schmidtchen, A., and Malmsten M., Crit. Rev. Biotechnol., 2012, vol. 32, pp. 143–171.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. 27.
    Schmidtchen, A., Pasupuleti, M., and Malmsten M., Adv. Colloid Interface Sci., 2014, vol. 205, pp. 265–274.CrossRefPubMedGoogle Scholar
  28. 28.
    Li, W., Tan, T., Xu, W., Xu, L., Dong, N., Ma, D., and Shan, A., Amino Acids, 2016, vol. 48, pp. 403–417.CrossRefPubMedGoogle Scholar
  29. 29.
    Teixeira, V., Feio, M. J., and Bastos, M., Prog. Lipid. Res., 2012, vol. 51, pp. 149–177.CrossRefPubMedGoogle Scholar
  30. 30.
    Khandelia, H. and Kaznessis, Y.N., J. Phys. Chem., 2007, vol. BIII, pp. 242–250.CrossRefGoogle Scholar
  31. 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. 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.CrossRefPubMedGoogle Scholar
  33. 33.
    Tani, A., Lee, S., Oishi, O., Aoyagi, H., and Ohno, M., J. Biochem., 1995, vol. 117, pp. 560–565.CrossRefPubMedGoogle Scholar
  34. 34.
    Fournier, J., Bruneau, C., Dixneuf, P.H., and Lécolier, S., J. Org. Chem., 1991, vol. 56, pp. 4456–4458.CrossRefGoogle Scholar
  35. 35.
    Wohlrab, A., Lamer, R., and VanNieuwenhze, M.S., J. Am. Chem. Soc., 2007, vol. 129, pp. 4175–4177.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Mhaske, S.B. and Argade, N.P., J. Org. Chem., 2001, vol. 66, pp. 9038–9040.CrossRefPubMedGoogle Scholar
  37. 37.
    Gowda, D.C., Gowda, B.K.K., and Rangappa, K.S., Synth. React. Inorg. Met. Org. Chem., 2001, vol. 31, pp. 1109–1110.CrossRefGoogle Scholar
  38. 38.
    Prasad, K.U., Iqbal, M.A., and Urry, D.W., Int. J. Pept. Protein. Res., 1985, vol. 25, pp. 408–413.CrossRefPubMedGoogle Scholar
  39. 39.
    Perez, C., Paul, M., and Bazerque, P., Acta. Biol. Med. Exp., 1990, vol. 15, pp. 113–115.Google Scholar
  40. 40.
    Singh, I. and Singh, V.P., Phytomorphology, 2000, vol. 50, pp. 151–157.Google Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • Kadallipura Puttaswamy Rakesh
    • 1
  • Suhas Ramesh
    • 2
  • Shivakumar
    • 1
  • Dase Channe Gowda
    • 1
  1. 1.Department of Studies in ChemistryUniversity of MysoreManasagangotri, MysuruIndia
  2. 2.Postgraduate Department of ChemistryJSS College of Arts, Commerce, and Science, B N RoadMysuruIndia

Personalised recommendations