The Ukrainian Biochemical Journal
ISSN 2409-4943
Journal archive > 2015 > N 1 January-February
SYNTHESIS, BIOLOGICAL EVALUATION AND DOCKING OF NOVEL
BISAMIDINOHYDRAZONES AS NON-PEPTIDE INHIBITORS OF FURIN

V. K. Kibirev1, T. V. Osadchuk2, O. P. Kozachenko2, V. Kholodovych3, O. D. Fedoryak2, V. S. Brovarets2

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.;
2Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Kyiv;
3Rutgers University, Newark, USA

A series of novel non-peptidic furin inhibitors with values of inhibitory constants (Ki) in the range of 0.74-1.54 μM was obtained by interactions of aminoguanidine hydrocarbonate with three diaryldicarbaldehydes. Correspondingly p-hydroquinone, piperazine and adipic acid were used as linkers between their benzene moieties. Docking studies of these new inhibitors into recently published 3D-structure of human furin (PDB code 4OMC) showed that they were able to interact with subsites S1 and S4 of the enzyme. The overall arrangement of bisamidinohydrazones into furin active site was similar to the position of the ligand co-crystallized with a protease. Observations obtained with molecular modeling allowed further guidance into chemical modifications of the synthesized inhibitors which improve their inhibitory activity.

Key words: furin, non-peptide inhibitors, bisamidinohydrasones, biological evaluation, docking.

The original article in English is available for download in PDF format.

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