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Design and synthesis of amino acids-conjugated heterocycle derived ureas/thioureas as potent inhibitors of protein glycation

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Abstract

Protein glycation is believed to play an important role in the development of long-term disorders associated with diabetic complications. In view of the wide occurrence of advanced glycation end products (AGE’s) and the oxidative stress derived from them in a variety of diabetic complications, it would be of great interest to identify and develop AGE inhibitors. In this study, synthesis and in vitro antiglycation activity of a small library of forty urea/thiourea derivatives of Phe/Tyr/Glu/Lys-benzisoxazole hybrids are reported. Structures of the compounds were confirmed by IR, NMR, mass spectrometry, and elemental analysis. Most of the title compounds exhibited promising activity. Best antiglycation activity was found for Tyr analogue with methoxy group as a substituent particularly at the para position with IC50 value of 1.9 μM against the positive control, Rutin, with IC50 = 41.9 μM. Thus, the title compounds represent novel class of potent antiglycating agents.

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Abbreviations

AGE’s:

advanced glycation end products

BSA:

bovine serum albumin

EDCI:

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

Het:

[3-(4-piperidyl)-6-fluoro-1,2-benzisoxazole]

HOBt:

1-hydroxybenzotriazole

NMM:

N-methyl morpholine

TCA:

trichloroacetic acid

References

  1. Rabbani, N. and Thornalley, P.J., Amino Acids, 2012, vol. 42, pp. 1087–1096.

    Article  CAS  PubMed  Google Scholar 

  2. Thorpe, S.R. and Baynes, J.W., Amino Acids, 2003, vol. 25, pp. 275–281.

    Article  CAS  PubMed  Google Scholar 

  3. Ahmed, N., Diabetes. Res. Clin. Pract., 2005, vol. 67, pp. 3–21.

    Article  CAS  PubMed  Google Scholar 

  4. Reddy, V.P. and Beyaz, A., Drug. Discov. Today, 2006, vol. 11, pp. 646–654.

    Article  CAS  PubMed  Google Scholar 

  5. Ramakrishnan, S. and Sulochana, K.N., Exp. Eye. Res., 1993, vol. 57, pp. 623–628.

    Article  CAS  PubMed  Google Scholar 

  6. Sensi, M., De Rossi, M.G., Celi, F.S., Cristina, A., Rosati, C., Prrett, D., Anreani, D., and Di Mario, U., Diabetologia, 1993, vol. 36, pp. 797–801.

    Article  CAS  PubMed  Google Scholar 

  7. Cao, F., Jia, J., Yin, Z., Gao, Y., Sha, L., Lai, Y., Ping, Q., and Zhang, Y., Mol. Pharm., 2012, vol. 9, pp. 2127–2135.

    CAS  PubMed  Google Scholar 

  8. Gupta, D., Gupta, S.V., Lee, K.D., and Amidon, G.L., Mol. Pharm., 2009, vol. 6, p. 1604–1611.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Hughes, R.A. and Moody, C.J., Angew. Chem. Int. Ed., 2007, vol. 46, pp. 7930–7954.

    Article  CAS  Google Scholar 

  10. Suresha, G.P., Prakasha, K.C., Shivakumara, K.N., Kapfo, W., and Gowda, D.C., Int. J. Pep. Res. Thera., 2009, vol. 15, pp. 25–30.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  12. Suresha, G.P., Suhas, R., Kapfo, W., and Gowda, D.C., Eur. J. Med. Chem., 2011, vol. 46, pp. 2530–2540.

    Article  CAS  PubMed  Google Scholar 

  13. Adams, A.D., Yuen, W., Hu, Z., Santini, C., Jones, A.B., MacNaul, K.L., Berger, J.P., Doebber, T.W., and Moller, D.E., Bioorg. Med. Chem. Lett., 2003, vol. 13, pp. 931–935.

    Article  CAS  PubMed  Google Scholar 

  14. Arakawa, K., Inamasu, M., Matsumoto, M., Okumara, K., Yasuda, K., Akastuka, H., Kawanami, S., Watanabe, A., Homma, K., Saiga, Y., Ozeki, M., and Iijima, I., Chem. Pharm. Bull., 1997, vol. 45, pp. 1984–1993.

    Article  CAS  PubMed  Google Scholar 

  15. Aiello, S., Wells, G., Stone, E.L., Kadri, H., Bazzi, R., Bell, D.R., Stevens, M.F., Matthews, C.S., Bradshaw, T.D., and Westwell, A.D., J. Med. Chem., 2008, vol. 51, pp. 5135–5139.

    Article  CAS  PubMed  Google Scholar 

  16. Suhas, R., Chandrashekar, S., and Gowda, D.C., Eur. J. Med. Chem., 2012, vol. 48, pp. 179–191.

    Article  CAS  PubMed  Google Scholar 

  17. Khan, K.M., Karim, A., Ambreen, N., Saied, S., Rasheed, S., Perveen, S., and Choudhary, M.I., J. Pharm. Res., 2012, vol. 5, pp. 664–665.

    Google Scholar 

  18. Khan, K.M., Saeed, S., Ali, M., Gohar, M., Zahid, J., Khan, A., Perveen, S., and Choudhary, M.I., Bioorg. Med. Chem., 2009, vol. 17, pp. 2447–2451.

    Article  CAS  PubMed  Google Scholar 

  19. Mendez, J.D., Xie, J., and Garcia-Perez, E., WASJ, 2007, vol. 2, pp. 090–098.

    Google Scholar 

  20. Venkatachalam, T.K., Maob, C., and Uckun, F.M., Bioorg. Med. Chem., 2004, vol. 12, pp. 4275–4284.

    Article  CAS  PubMed  Google Scholar 

  21. Tale, R.H., Rodge, A.H., Hatnapure, G.D., Keche, A.P., Patil, K.M., and Pawar, R.P., Med. Chem. Res., 2012, vol. 21, pp. 4252–4260.

    Article  CAS  Google Scholar 

  22. Suhas, R., Chandrashekar, S., and Gowda, D.C., Int. J. Pep. Res. Thera., 2012, vol. 18, pp. 89–98.

    Article  CAS  Google Scholar 

  23. Suhas, R. and Gowda, D.C., Chem. Biol. Drug. Des., 2012, vol. 79, pp. 850–862.

    Article  CAS  PubMed  Google Scholar 

  24. Perveen, S., Fatima, N., Khan, M.A., Dar, A., Khan, K.M., Afza, N., and Voelter, W., Med. Chem. Res., 2012, vol. 21, pp. 2709–2715.

    Article  CAS  Google Scholar 

  25. Rahbar, S. and Figarola, J.L., Arch. Biochem. Biophys., 2003, vol. 419, pp. 63–79.

    Article  CAS  PubMed  Google Scholar 

  26. Strupczewski, J.T., Allen, R.C., Gardner, B.A., Schmid, B.L., Stache, U., Glamkowski, E.J., and Jones, M.C., J. Med. Chem., 1985, vol. 28, pp. 761–769.

    Article  CAS  PubMed  Google Scholar 

  27. Shantharam, C.S., Suyoga Vardhan, D.M., Suhas, R., Sridhara, M.B., and Gowda, D.C., Eur. J. Med. Chem., 2013, vol. 60, pp. 325–332.

    Article  CAS  PubMed  Google Scholar 

  28. Nakagawa, T., Yokozawa, T., Terasawa, K., Shu, S., and Juneja, L.R., J. Agric. Food. Chem., 2002, vol. 50, pp. 2418–2422.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

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

    C. S. Shantharam, D. M. Suyoga Vardhan, R. Suhas & D. Channe Gowda

Authors
  1. C. S. Shantharam
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  2. D. M. Suyoga Vardhan
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  3. R. Suhas
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  4. D. Channe Gowda
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Correspondence to D. Channe Gowda.

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Shantharam, C.S., Suyoga Vardhan, D.M., Suhas, R. et al. Design and synthesis of amino acids-conjugated heterocycle derived ureas/thioureas as potent inhibitors of protein glycation. Russ J Bioorg Chem 40, 443–454 (2014). https://doi.org/10.1134/S1068162014040128

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  • DOI: https://doi.org/10.1134/S1068162014040128

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