Calix[4]arene α-hydroxymethylphosphonic acids as potential inhibitors of protein tyrosine phosphatases

V. V. Trush, V. Yu. Tanchuk, S. O. Cherenok, V. I. Kalchenko, A. I. Vovk

Abstract


Calix[4]arene are known to be a promising scaffold for designing inhibitors of protein tyrosine phosphatases.
In this work calix[4]arene mono- and bis-α-hydroxymethylphosphonic acids have been tested in vitro for the inhibitory activity against some therapeutically important protein tyrosine phosphatases. The results obtained have shown that these macrocyclic compounds can inhibit CD45, PTP1B, and SHP2 with IC50 values in the micromolar range. At the same time the inhibitors have demonstrated lower activity toward other protein tyrosine phosphatases such as TC-PTP and PTPβ. It has been found that mono-substituted calix[4]arene is more potent inhibitor of CD45 than the bis-substituted one and shows about 2-15 fold selectivity over TC-PTP, PTPβ, SHP2 and PTP1B. Model 4-hydroxyphenyl-α-hydroxymethylphosphonate displays at least one order lower activity than the phosphonate derivatives of calix[4]arene. Thus, the combination of a macrocyclic platform and α-hydroxymethylphosphonate group is essential for the inhibition activities of these compounds. Computer-simulated docking studies have been performed using AutoDock 4.2 programme by the example of PTP1B. The data obtained indicate that the inhibitors can bind in the active site of the enzyme. To clarify the inhibition mechanism the possible enzyme-inhibitor complexes have been considered using several crystal structures of PTP1B and all stereoisomeric forms of the inhibitors.


Keywords


protein tyrosine phosphatases; inhibitors; calixarenes; docking

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Vintonyak V.V., Antonchick A.P., Rauh D. et al. Curr. Opin. Chem. Biol., 2009, Vol. 13, pp.272-283.

Alonso A., Sasin J., Bottini N. et al. Cell., 2004, Vol. 117, pp.699-711.

Hunter T. Cell., 2004, Vol. 100, pp.113-127.

Elchebly M., Payette P., Michaliszyn E. et al. Science, 1999, Vol. 283, pp.1544-1548.

Klaman L.D., Boss O., Peroni O.D. et al. Mol. Cell Biol., 2000, Vol. 20, No.15, pp.5479-5489.

Lund I.K., Hansen J.A., Andersen H.S. et al. J. Mol. Endocrinol., 2005, Vol. 34, No.2, pp.339-351.

Wang S., Yu W.-M., Zhang W. et al. J. Biol. Chem., 2009, Vol. 284, No.2, pp.913-920.

Chan G., Kalaitzidis D., Neel B.G. Cancer Metastasis Rev., 2008, Vol. 27, No.2, pp.179-192.

Hatakeyama M. Nat. Rev. Cancer., 2004, Vol. 4, pp.688-694.

Koretzky G.A., Picus J., Thomas M.L. et al. Nature., 1990, Vol. 346, pp.66-68.

Justement L.B., Campbell K.S., Chien N.C. et al. Science, 1991, Vol. 252, pp.1839-1842.

Mustelin T., Coggeshall K.M., Altman A. Proc. Natl. Acad. Sci., 1989, Vol. 86, pp.6302-6306.

Desai D.M., Sap J., Silvennoinen O. et al. EMBO J., 1994, Vol. 13, pp.4002-4010.

Lazarovits A.I., Visser L., Asfar S. et al. Kidney Int., 1999, Vol. 55, pp.1303-1310.

Sansone F., Segura M., Ungaro R. Dodrecht: Kluwer Academic Publishers, 2001, pp.496-512.

Vicens J., Harrowfield J., Baklouti L. Dodrecht: Springer, 2007, pp.395-340.

Perret F., Lazar A.N., Coleman A.W. Chem. Commun., 2006, pp.2425-2438.

Guo D.-D., Wang K., Liu Y. J. Incl. Phenom. Macrocycl. Chem., 2008, Vol. 62, pp.1-21.

Casnati A., Fabbi M., Pelizzi N. et al. Bioorg. Med. Chem. Lett., 1996, Vol. 6, pp.2699-2704.

Dibama H.M., Clarot I., Fontanay S. et al. Bioorg. Med. Chem. Lett., 2009, Vol. 19, pp.2679-2682.

Patel M.B., Modi N.R., Raval J.P. et al. Org. Biomol. Chem., 2012, Vol. 10, pp.1785-1789.

Tsou L.K., Dutschman G.E., Gullen E.A. et al. Bioorg. Med. Chem. Lett., 2010, Vol. 20, pp.2137-2139.

Mourer M., Psychogios N., Laumond G. et al. Bioorg. Med. Chem., 2010, Vol. 18, pp.36-40.

Menger F.M., Bian J., Sizova E. et al. Org. Lett., 2004, Vol. 6, pp.261-264.

Shimojo K., Oshima T., Naganawa H. et al. Biomacromolecules, 2007, Vol. 8, pp.3061-3066.

Rodik R.V., Boyko V.I., Kalchenko V.I. Curr. Med. Chem., 2009, Vol. 16, pp.1630-1655.

Li X., Bhandari A., Holmes C. P. et al. Bioorg. Med. Chem. Lett., 2004, Vol. 14, pp.4301-4305.

Wang Q., Zhu M., Zhu R. et al. Eur. J. Med. Chem., 2012, Vol. 49, pp.354-360.

Vovk A.I., Kalchenko V.I., Cherenok S.O. et al. Org. Biomol. Chem., 2004, Vol. 2, pp.3162-3166.

Vovk A.I., Kononets L.A., Tanchuk V.Yu. et al. J. Incl. Phenom. Macrocycl. Chem., 2010, Vol. 66, pp.271-276.

Cherenok S.O., Vovk A.I., Muravyova I.V. et al. Org. Lett., 2006, Vol. 8, pp.549-556.

Vovk A.I., Kononets L.A., Tanchuk V.Yu. et al. Bioorg. Med. Chem. Lett., 2010, Vol. 20, pp.483-485.

Trush V.V., Cherenok S.O., Tanchuk V.Yu. et al. Bioorg. Med. Chem. Lett., 2013, Vol. 23, No.22, pp.5619-5623.

Patel D.V., Rielly-Gauvin K., Ryono D.E. et al. J. Med. Chem., 1995, Vol. 38, pp.4557-4569.

Bubenik M., Preville P., Dugas J. et al. Tetrahedron Lett., 2003, Vol. 44, pp.8261-8263.

Patel R.N., Banerjee A., Szarka L.J. Tetrahedron: Asymmetry, 1997, Vol. 8, pp.1055-1059.

Patel D.V., Rielly-Gauvin K., Ryono D.E. Tetrahedron Lett., 1990, Vol. 31, pp.5587-5590.

Frechette R.F., Ackerman C., Beers S. et al. Bioorg. Med. Chem. Lett., 1997, Vol. 7, No.17, pp.2169-2172.

Cherenok S.O., Yushchenko O.A., Tanchuk V.Yu. et al. Arkivok, 2012, Vol. 4, pp.278-280.

Tonks N.K. FEBS Lett., 2003, Vol. 546, pp.140-148.

Denu J.M., Dixon J.E. Curr. Opin. Chem. Biol., 1998, Vol. 2, pp.633- 641.

Kamerlin S.C.L., Rucker R., Boresch S. Biochem. Biophys. Res. Comm., 2006, Vol. 345, pp.1161-1166.

Tanchuk V.Y., Tanin V.O., Vovk A.I. Chem. Biol. Drug Des., 2012, Vol. 80, pp.121-124.

Huey R., Morris G.M., Olson A.J. et al. J. Comput. Chem., 2007, Vol. 28, No.6, pp.1145-1152.


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DOI: https://doi.org/10.24959/ophcj.14.782

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