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

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