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.
Similar content being viewed by others
Abbreviations
- DPP-4:
-
dipeptidyl peptidase 4
References
Liu, Y. and Hu, Y., Future Med. Chem., 2014, vol. 6, no. 7, pp. 793–808.
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.
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.
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.
Lagunin, A., Stepanchikova, A., Filimonov, D., and Poroikov, V., Bioinformatics, 2000, vol. 16, no. 8, pp. 747–748.
Trott, O. and Olson, A.J., J. Comput. Chem., 2009, vol. 31, no. 2, pp. 455–461.
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.
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.
Vassiliev, P.M., in 2nd Russ. Conf. Med. Chem. B. Abstr. (Novosibirsk, Russia, July 5–10, 2012), 2012, p. 302.
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.
Pi-Sunyer, F.X., Schweizer, A., Mills, D., and Dejager, S., Diabetes Res. Clin. Pract., 2007, vol. 76, no. 1, pp. 132–138.
Liu, J., Huan, Y., Li, C., Liu, M., and Shen, Z., Acta Pharm. Sin., vol. 4, no. 2, pp. 135–140.
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.
Klimochkin, Yu.N., Bagrii, E.I., Dolgopolova, T.N., and Moiseev, I.K., Russ. Chem. Bull., 1988, vol.37, no. 4, pp. 757–759.
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.
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.
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.
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.
Wanka, L., Cabrele, C., Vanejews, M., and Schreiner, P.R., Eur. J. Org. Chem., 2007, vol. 2007, no. 9, pp. 1474–1490.
Makarova, N.V., Zemtsova, M.N., and Moiseev, I.K., Chem. Heterocycl. Compd., 1994, vol. 30, no. 5, pp. 544–546.
Fischer, W. and Grob, C.A., Helv. Chim. Acta, 1978, vol. 61, no. 5, pp. 1588–1608.
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.
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.
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.
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.
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.
Baimuratov, M.R., Leonova, M.V., Shiryaev, V.A., and Klimochkin, Y.N., Tetrahedron Lett., 2016, vol. 57, no. 48, pp. 5317–5320.
Author information
Authors and Affiliations
Corresponding author
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
About this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1068162017040124