Evaluation of bisbenzamidines as inhibitors for matriptase-2

被引：6

作者：

Beckmann, Anna-Madeleine ^{[1
]}

Gilberg, Erik ^{[1
,2
]}

Gattner, Susanne ^{[1
]}

Huang, Tien L. ^{[3
]}

Eynde, Jean Jacques Vanden ^{[3
]}

Mayence, Annie ^{[3
]}

Bajorath, Juergen ^{[2
]}

Stirnberg, Marit ^{[1
]}

Guetschow, Michael ^{[1
]}

机构：

[1] Univ Bonn, Pharmaceut Chem 1, Inst Pharmaceut, Immenburg 4, D-53121 Bonn, Germany

[2] Univ Bonn, LIMES Program Unit Chem Biol & Med Chem, B IT, Dept Life Sci Informat, Dahlmannstr 2, D-53113 Bonn, Germany

[3] Xavier Univ Louisiana, Coll Pharm, Dept Basic Pharmaceut Sci, 1 Drexel Dr, New Orleans, LA 70125 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 15期

关键词：

Bisbenzamidines; Matriptase-2; Serine proteases; BETA-THALASSEMIA; SELECTIVE INHIBITORS; TRYPANOCIDAL ACTIVITY; PENTAMIDINE ANALOGS; BIS-BENZAMIDINES; SERINE PROTEASES; CLEAVAGE SITES; IRON OVERLOAD; FACTOR XA; TRYPSIN;

D O I：

10.1016/j.bmcl.2016.05.071

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The serine protease matriptase-2 has attracted much attention as a potential target for the treatment of iron overload diseases. In this study, a series of 27 symmetric, achiral bisbenzamidines was evaluated for inhibitory activity against human matriptase-2, against the closely related enzyme human matriptase, as well as against human thrombin, bovine factor Xa and human trypsin. The conformationally restricted piperazine derivative 19 and the oxamide-derived bisbenzamidine 1 were identified as the most potent inhibitors of this series for matriptase-2 and matriptase, respectively. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：3741 / 3745

页数：5

共 45 条

[1] En Route to New Therapeutic Options for Iron Overload Diseases: Matriptase-2 as a Target for Kunitz-Type Inhibitors [J].

Beckmann, Anna-Madeleine ;

Maurer, Eva ;

Luelsdorff, Verena ;

Wilms, Annika ;

Furtmann, Norbert ;

Bajorath, Juergen ;

Guetschow, Michael ;

Stirnberg, Marit .

CHEMBIOCHEM, 2016, 17 (07) :595-604

[2] Probing the substrate specificities of matriptase, matriptase-2, hepsin and DESC1 with internally quenched fluorescent peptides [J].

Beliveau, Francois ;

Desilets, Antoine ;

Leduc, Richard .

FEBS JOURNAL, 2009, 276 (08) :2213-2226

[3] Pentamidine analogs as inhibitors of [3H]MK-801 and [3H]ifenprodil binding to rat brain NMDA receptors [J].

Berger, Michael L. ;

Maciejewska, Dorota ;

Vanden Eynde, Jean Jacques ;

Mottamal, Madhusoodanan ;

Zabinski, Jerzy ;

Kazmierczak, Pawel ;

Rezler, Mateusz ;

Jarak, Ivana ;

Piantanida, Ivo ;

Karminski-Zamola, Grace ;

Mayence, Annie ;

Rebernik, Patrick ;

Kumar, Arvind ;

Ismail, Mohamed A. ;

Boykin, David W. ;

Huang, Tien L. .

BIOORGANIC & MEDICINAL CHEMISTRY, 2015, 23 (15) :4489-4500

[4] Fluorescence-Labeled Bis-benzamidines as Fluorogenic DNA Minor-Groove Binders: Photophysics and Binding Dynamics [J].

Bordello, Jorge ;

Sanchez, Mateo I. ;

Vazquez, M. Eugenio ;

Mascarenas, Jose L. ;

Al-Soufi, Wajih ;

Novo, Mercedes .

CHEMISTRY-A EUROPEAN JOURNAL, 2015, 21 (04) :1609-1619

[5] Design and Synthesis of Potent, Selective Inhibitors of Matriptase [J].

Colombo, Eloic ;

Desilets, Antoine ;

Duchene, Dominic ;

Chagnon, Felix ;

Najmanovich, Rafael ;

Leduc, Richard ;

Marsault, Eric .

ACS MEDICINAL CHEMISTRY LETTERS, 2012, 3 (07) :530-534

[6] Understanding binding selectivity toward trypsin and factor Xa: the role of aromatic interactions [J].

Di Fenza, Armida ;

Heine, Andreas ;

Koert, Ulrich ;

Klebe, Gerhard .

CHEMMEDCHEM, 2007, 2 (03) :297-308

[7] Trypanocidal activity of conformationally restricted pentamidine congeners [J].

Donkor, IO ;

Huang, TL ;

Tao, B ;

Rattendi, D ;

Lane, S ;

Vargas, M ;

Goldberg, B ;

Bacchi, C .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (06) :1041-1048

[8] Active site mapping of trypsin, thrombin and matriptase-2 by sulfamoyl benzamidines [J].

Dosa, Stefan ;

Stirnberg, Marit ;

Luelsdorff, Verena ;

Haeussler, Daniela ;

Maurer, Eva ;

Guetschow, Michael .

BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (21) :6489-6505

[9] Analysis of Subpocket Selectivity and Identification of Potent Selective Inhibitors for Matriptase and Matriptase-2 [J].

Duchene, Dominic ;

Colombo, Eloic ;

Desilets, Antoine ;

Boudreault, Pierre-Luc ;

Leduc, Richard ;

Marsault, Eric ;

Najmanovich, Rafael .

JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (23) :10198-10204

[10] Structure-based approach for the discovery of bis-benzamidines as novel inhibitors of matriptase [J].

Enyedy, IJ ;

Lee, SL ;

Kuo, AH ;

Dickson, RB ;

Lin, CY ;

Wang, SM .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (09) :1349-1355

← 1 2 3 4 5 →