Skip to main content
Log in

New dipeptidyl peptidase 4 inhibitors among adamantane derivatives

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

Abstract

Fifteen adamantane derivatives were synthesized. Preliminary evaluation of their potential as dipeptidyl peptidase 4 (DPP-4) inhibitors was performed in silico by the Microcosm informational technology, PASS system, and docking in AutoDock Vina. The DPP-4 inhibition was studied in vitro. The selectivity of action of the most active compounds was studied by the direct inhibition of human plasma DPP-4 and recombinant human DPP-8. The highest activity was found for the compounds containing a nitrogen atom in the β-position of the side chain, namely, derivatives of adamantane carboxylic acid and N-(3-adamantyl-allyl) thiourea. We demonstrated that the most active compound of the series, 3,5-dimethyladamantane 1-carboxamide, was a selective DPP-4 inhibitor with IC50 53.94 μM.

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

Access this article

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

DPP-4:

dipeptidyl peptidase 4

References

  1. Liu, Y. and Hu, Y., Future Med. Chem., 2014, vol. 6, no. 7, pp. 793–808.

    Article  CAS  PubMed  Google Scholar 

  2. Mu, J., Woods, J., Zhou, Y.P., Roy, R.S., Li, Z., Zycband, E., Feng, Y., Zhu, L., Li, C., Howard, A.D., et al., Diabetes, 2006, vol. 55, no. 6, pp. 1695–1704.

    Article  CAS  PubMed  Google Scholar 

  3. Vassiliev, P.M., Spasov, A.A., Kosolapov, V.A., Kucheryavenko, A.F., Gurova, N.A., and Anisimova, V.A., Application of Computational Techniques in Pharmacy and Medicine, Dordrecht: Springer Netherlands, 2014, pp. 369–431.

    Google Scholar 

  4. Vassiliev, P.M., Spasov, A.A., Chepljaeva, N.I., Zagrebelnaya, O.V., Taran, A.S., and Anisimova, V.A., in Abstr. XXII Russ. Natl. Congr. “Human Drug,” 2014, p. 215.

    Google Scholar 

  5. Lagunin, A., Stepanchikova, A., Filimonov, D., and Poroikov, V., Bioinformatics, 2000, vol. 16, no. 8, pp. 747–748.

    Article  CAS  PubMed  Google Scholar 

  6. Trott, O. and Olson, A.J., J. Comput. Chem., 2009, vol. 31, no. 2, pp. 455–461.

    Google Scholar 

  7. Taran, A.S., Vassiliev, P.M., Spasov, A.A., Chepljaeva, N.I., Popov, Y., Lobasenko, V., Shishkin, E., and Mokhov, V., in 2nd Russ. Conf. Med. Chem. B. Abstr. (Novosibirsk, Russia, July 5–10, 2012), 2012, p. 285.

    Google Scholar 

  8. Vassiliev, P.M., Spasov, A.A., Chepljaeva, N.I., and Litvinov, R.A., Database no. 2015620158, Dipeptidyl peptidase-4 inhibitors, RF Patent no. 2014621771, 2015.

    Google Scholar 

  9. Vassiliev, P.M., in 2nd Russ. Conf. Med. Chem. B. Abstr. (Novosibirsk, Russia, July 5–10, 2012), 2012, p. 302.

    Google Scholar 

  10. Matheeussen, V., Lambeir, A.-M., Jungraithmayr, W., Gomez, N., Mc Entee, K., Van der Veken, P., Scharpé, S., and De Meester, I., Clin. Chim. Acta, 2012, vol. 413, nos. 3–4, pp. 456–462.

    Article  CAS  PubMed  Google Scholar 

  11. Pi-Sunyer, F.X., Schweizer, A., Mills, D., and Dejager, S., Diabetes Res. Clin. Pract., 2007, vol. 76, no. 1, pp. 132–138.

    Article  CAS  PubMed  Google Scholar 

  12. Liu, J., Huan, Y., Li, C., Liu, M., and Shen, Z., Acta Pharm. Sin., vol. 4, no. 2, pp. 135–140.

  13. Moiseev, I.K. and Klimochkin, Yu.N., Method for obtaining of adamantine acylamino derivatives, USSR Inventor’s Certificate no. 1197393, Bull. Izobret., 2006, no. 26.

  14. Klimochkin, Yu.N., Bagrii, E.I., Dolgopolova, T.N., and Moiseev, I.K., Russ. Chem. Bull., 1988, vol.37, no. 4, pp. 757–759.

    Article  Google Scholar 

  15. Fresno, N., Pérez-Fernández, R., Goicoechea, C., Alkorta, I., Fernández-Carvajal, A., de laTorre-Martínez, R., Quirce, S., Ferrer-Montiel, A., Martín, M.I., Goya, P., et al., PLoS One, 2014, vol. 9, no. 12, p. e113841.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Klimochkin, Yu.N., Moiseev, I.K., Boreko, E.I., Vladyko, G.V., and Korobchenko, L.V., Pharm. Chem. J., 1989, vol.23, no. 4, pp. 304–307.

    Article  Google Scholar 

  17. Novakov, I.A., Kulev, I.A., Radchenko, S.S., Birznieks, K.A., Boreko, E.I., Vladyko, G.V., and Korobchenko, L.V., Pharm. Chem. J., 1987, vol. 21, no. 4, pp. 287–291.

    Article  Google Scholar 

  18. Novikov, S.S., Khardin, A.P., Butenko, L.N., Kulev, I.A., Novakov, I.A., Radchenko, S.S., and Burdenko, S.S., Zh. Org. Khim., 1980, vol. 16, no. 7, pp. 1433–1435.

    CAS  Google Scholar 

  19. Wanka, L., Cabrele, C., Vanejews, M., and Schreiner, P.R., Eur. J. Org. Chem., 2007, vol. 2007, no. 9, pp. 1474–1490.

    Article  Google Scholar 

  20. Makarova, N.V., Zemtsova, M.N., and Moiseev, I.K., Chem. Heterocycl. Compd., 1994, vol. 30, no. 5, pp. 544–546.

    Article  Google Scholar 

  21. Fischer, W. and Grob, C.A., Helv. Chim. Acta, 1978, vol. 61, no. 5, pp. 1588–1608.

    Article  CAS  Google Scholar 

  22. Ajami, K., Abbott, C.A., Obradovic, M., Gysbers, V., Kähne, T., McCaughan, G.W., and Gorrell, M.D., Biochemistry, 2003, vol. 42, no. 3, pp. 694–701.

    Article  CAS  PubMed  Google Scholar 

  23. Lankas, G.R., Leiting, B., Roy, R.S., Eiermann, G.J., Beconi, M.G., Biftu, T., Chan, C.-C., Edmondson, S., Feeney, W.P., He, H., et al., Diabetes, 2005, vol. 54, no. 10, pp. 2988–2994.

    Article  CAS  PubMed  Google Scholar 

  24. Burkey, B.F., Hoffmann, P.K., Hassiepen, U., Trappe, J., Juedes, M., and Foley, J.E., Diabetes Obes. Metab., 2008, vol. 10, no. 11, pp. 1057–1061.

    Article  CAS  PubMed  Google Scholar 

  25. Metzler, W.J., Yanchunas, J., Weigelt, C., Kish, K., Klei, H.E., Xie, D., Zhang, Y., Corbett, M., Tamura, J.K., He, B., et al., Protein Sci., 2008, vol. 17, no. 2, pp. 240–250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nabeno, M., Akahoshi, F., Kishida, H., Miyaguchi, I., Tanaka, Y., Ishii, S., and Kadowaki, T., Biochem. Biophys. Res. Commun., 2013, vol. 434, no. 2, pp. 191–196.

    Article  CAS  PubMed  Google Scholar 

  27. Baimuratov, M.R., Leonova, M.V., Shiryaev, V.A., and Klimochkin, Y.N., Tetrahedron Lett., 2016, vol. 57, no. 48, pp. 5317–5320.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yu. N. Klimochkin.

Additional information

Original Russian Text © A.A. Spasov, P.M. Vasil’ev, D.A. Babkov, T.Yu. Prokhorova, E.A. Sturova, Yu.N. Klimochkin, M.V. Leonova, M.R. Baimuratov, 2017, published in Bioorganicheskaya Khimiya, 2017, Vol. 43, No. 4, pp. 420–426.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Spasov, A.A., Vasil’ev, P.M., Babkov, D.A. et al. New dipeptidyl peptidase 4 inhibitors among adamantane derivatives. Russ J Bioorg Chem 43, 449–455 (2017). https://doi.org/10.1134/S1068162017040124

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1068162017040124

Keywords

Navigation