Russian Journal of Bioorganic Chemistry

, Volume 34, Issue 1, pp 60–66

Inhibition of alkaline phosphatase by thioureido derivatives of methylenebisphosphonic acid

Authors

    • Institute of Bioorganic Chemistry and PetrochemistryNational Academy of Sciences of Ukraine
  • A. L. Chuiko
    • Institute of Organic ChemistryNational Academy of Sciences of Ukraine
  • L. A. Kononets
    • Institute of Bioorganic Chemistry and PetrochemistryNational Academy of Sciences of Ukraine
  • V. Yu. Tanchuk
    • Institute of Bioorganic Chemistry and PetrochemistryNational Academy of Sciences of Ukraine
  • I. V. Murav’eva
    • Institute of Bioorganic Chemistry and PetrochemistryNational Academy of Sciences of Ukraine
  • M. O. Lozinsky
    • Institute of Organic ChemistryNational Academy of Sciences of Ukraine
  • V. P. Kukhar
    • Institute of Bioorganic Chemistry and PetrochemistryNational Academy of Sciences of Ukraine
Article

DOI: 10.1134/S1068162008010081

Cite this article as:
Vovk, A.I., Chuiko, A.L., Kononets, L.A. et al. Russ J Bioorg Chem (2008) 34: 60. doi:10.1134/S1068162008010081
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Abstract

A series of thioureido derivatives of methylenebisphosphonic acid were synthesized by the reaction of aminomethylenebisphosphonic acid with the corresponding isothiocyanates, and their effect on the activity of alkaline phosphatases from bovine small intestine mucosa (BSIM) and human placenta was studied. It was found that (3-phenylthioureido)methylenebisphosphonate is approximately one order of magnitude more effective in inhibiting the activity of alkaline phosphatase from BSIM than the alkyl derivatives of thioureidomethylenebisphosphonic acid with methyl, ethyl, tert-butyl, or cyclohexyl substituents. The introduction of substituents into the benzene ring of (3-phenylthioureido)methylenebisphosphonate decreased the effect of the inhibitor on the activity of the enzyme. The affinity of (3-phenylureido)methylenebisphosphonate to the alkaline phosphatase of BSIM was also weaker as compared with the corresponding thioureidomethylenebisphosphonate. The insertion of thioureidobisphosphonates into the active site of alkaline phosphatase of human placenta by the method of molecular docking indicated that the methylenebisphosphonate residue and the substituted amino groups of the inhibitor are involved in the mechanisms of complex formation with the enzyme. It is supposed that the improvement of the inhibitory activity of (3-phenylthioureido)methylenebisphosphonate toward alkaline phosphatase of BSIM is due to the additional fixation of the phenyl substituent in the active site of the enzyme.

Key words

alkaline phosphataseinhibitionmolecular dockingthioureidomethylenebisphosphonates

Abbreviations

BSIM

bovine small intestine mucosa

HP

human placenta

Copyright information

© Pleiades Publishing, Ltd. 2008