Effect of cyanopyrrolidine derivatives on the activity of prolylendopeptidase, acute exudative inflammation and visceral pain in mice

   
Ivanova E.A.1 , Zolotov N.N.1, Pozdnev V.F.2, Voronina T.A.1

1. Zakusov Institute of Pharmacology, Moscow, Russia
2. Institute of Biomedical Chemistry, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20206601077      PubMed Id: 32116229
Year: 2020  Volume: 66  Issue: 1  Pages: 77-82
Cyanopyrrolidine derivatives benzyloxycarbonyl-methionyl-cyanopyrrolidine (ZMetPrdN), benzyloxycarbonylphenylalanyl- cyanopyrrolidine (ZPhePrdN), tert-butyl-hydroxycarbonyl-glycyl-cyanopyrrolidine (BocGlyPrdN), tert-butyl-hydroxycarbonyl-methionyl-cyanopyrrolidine (BocMetPrdN) are inhibitors of prolylendopeptidase (PREP; EC 3.4.21.26) with an IC50 of 2 nM to 12 nM. ZMetPrdN, ZPhePrdN and BocMetPrdN additionally inhibited dipeptidyl peptidase IV (DPP-4; EC 3.4.14.5) with an IC50 of 1100 nM to 3200 nM. All the compounds have antinociceptive properties in the acetic acid writhing test in mice. But only cyanopyrrolidine derivatives with aromatic substituents decrease exudative inflammation. The cyanopyrrolidine derivatives also increase PREP activity and compensatorily reduce DPP-4 activity in the serum of mice three hours after the induction of inflammation. Thus, cyanopyrrolidine derivatives exhibit antinociceptive and antiexudative properties in part via their effect on PREP.
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Keywords: cyanopyrrolidine derivatives, prolylendopeptidase, dipeptidyl peptidase IV, inflammation, acetic acid-induced peritonitis, visceral pain
Citation:

Ivanova, E. A., Zolotov, N. N., Pozdnev, V. F., Voronina, T. A. (2020). Effect of cyanopyrrolidine derivatives on the activity of prolylendopeptidase, acute exudative inflammation and visceral pain in mice. Biomeditsinskaya khimiya, 66(1), 77-82.
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