2-Oxoamide inhibitors of phospholipase A2 activity and cellular arachidonate release based on dipeptides and pseudodipeptides

被引：17

作者：

Barbayianni, Efrosini ^{[3
]}

Stephens, Daren ^{[1
,2
]}

Grkovich, Andrej ^{[1
,2
]}

Magrioti, Victoria ^{[3
]}

Hsu, Yuan-Hao ^{[1
,2
]}

Dolatzas, Panagiotis ^{[3
]}

Kalogiannidis, Dimitrios ^{[3
]}

Dennis, Edward A. ^{[1
,2
]}

Kokotos, George ^{[3
]}

机构：

[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Sch Med, Dept Pharmacol, La Jolla, CA 92093 USA

[3] Univ Athens, Organ Chem Lab, Dept Chem, Athens 15771, Greece

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 13期

关键词：

Dipeptides; Inhibitors; 2-Oxoamides; Phospholipase A(2); Pseudodipeptides; ONE-POT CONVERSION; GROUP-IVA; AMINO-ACIDS; GROUP-V; PSEUDOPEPTIDE ANALOGS; BIOLOGICAL EVALUATION; GROUP-IIA; ALCOHOLS; CELLS; OXIDATION;

D O I：

10.1016/j.bmc.2009.03.069

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of 2-oxoamides based on dipeptides and pseudodipeptides were synthesized and their activities towards two human intracellular phospholipases A(2) (GIVA cPLA(2) and GVIA iPLA(2)) and one human secretory phospholipase A(2) (GV sPLA(2)) were evaluated. Derivatives containing a free carboxyl group are selective GIVA cPLA(2) inhibitors. A derivative based on the ethyl ester of an ether pseudodipeptide is the first 2-oxoamide, which preferentially inhibits GVIA iPLA2. The effect of 2-oxoamides on the generation of arachidonic acid from RAW 264.7 macrophages was also studied and it was found that selective GIVA cPLA(2) inhibitors preferentially inhibited cellular arachidonic acid release; one pseudodipeptide gave an IC50 value of 2 mu M. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：4833 / 4843

页数：11

共 40 条

[1] Polyamide based nucleic acid analogs - Synthesis of delta-amino acids with nucleic acid bases bearing side chains [J].

Altmann, KH ;

Chiesi, CS ;

GarciaEcheverria, C .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1997, 7 (09) :1119-1122

[2] Synthesis of 2-oxoamides based on sulfonamide analogs of γ-amino acids and their activity on phospholipase A2 [J].

Antonopoulou, Georgia ;

Magrioti, Victoria ;

Stephens, Daren ;

Constantinou-Kokotou, Violetta ;

Dennis, Edward A. ;

Kokotos, George .

JOURNAL OF PEPTIDE SCIENCE, 2008, 14 (10) :1111-1120

[3] Structure-activity relationships of natural and non-natural amino acid-based amide and 2-oxoamide inhibitors of human phospholipase A2 enzymes [J].

Antonopoulou, Georgia ;

Barbayianni, Efrosini ;

Magrioti, Victoria ;

Cotton, Naomi ;

Stephens, Daren ;

Constantinou-Kokotou, Violetta ;

Dennis, Edward A. ;

Kokotos, George .

BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (24) :10257-10269

[4] Cellular regulation and proposed biological functions of group VIA calcium-independent phospholipase A2 in activated cells [J].

Balsinde, J ;

Balboa, MA .

CELLULAR SIGNALLING, 2005, 17 (09) :1052-1062

[5] Synthesis of Polyfluoro Ketones for Selective Inhibition of Human Phospholipase A2 Enzymes [J].

Baskakis, Constantinos ;

Magrioti, Victoria ;

Cotton, Naomi ;

Stephens, Daren ;

Constantinou-Kokotou, Violetta ;

Dennis, Edward A. ;

Kokotos, George .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (24) :8027-8037

[6] TLR-4 and sustained calcium agonists synergistically produce eicosanoids independent of protein synthesis in RAW264.7 cells [J].

Buczynski, Matthew W. ;

Stephens, Daren L. ;

Bowers-Gentry, Rebecca C. ;

Grkovich, Andrej ;

Deems, Raymond A. ;

Dennis, Edward A. .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (31) :22834-22847

[7] Synthesis and study of a lipophilic α-keto amide inhibitor of pancreatic lipase [J].

Chiou, A ;

Markidis, T ;

Constantinou-Kokotou, V ;

Verger, R ;

Kokotos, G .

ORGANIC LETTERS, 2000, 2 (03) :347-350

[8] Synthesis and activity of 2-oxoamides containing long chain β-amino acids [J].

Constantinou-Kokotou, V ;

Peristeraki, A ;

Kokotos, CG ;

Six, DA ;

Dennis, EA .

JOURNAL OF PEPTIDE SCIENCE, 2005, 11 (07) :431-435

[9] Detection and quantitation of eicosanoids via high performance liquid chromatography-electrospray ionization-mass spectrometry [J].

Deems, Raymond ;

Buczynski, Matthew W. ;

Bowers-Gentry, Rebecca ;

Harkewicz, Richard ;

Dennis, Edward A. .

LIPIDOMICS AND BIOACTIVE LIPIDS: MASS-SPECTROMETRY-BASED LIPID ANALYSIS, 2007, 432 :59-82

[10] A USEFUL 12-I-5 TRIACETOXYPERIODINANE (THE DESS-MARTIN PERIODINANE) FOR THE SELECTIVE OXIDATION OF PRIMARY OR SECONDARY ALCOHOLS AND A VARIETY OF RELATED 12-I-5 SPECIES [J].

DESS, DB ;

MARTIN, JC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1991, 113 (19) :7277-7287

← 1 2 3 4 →