2-Oxoamides based on dipeptides as selective calcium-independent phospholipase A2 inhibitors. Issue 3 (1st February 2017)

• Record Type: Journal Article
• Authors: Smyrniotou, Anneta; Kokotou, Maroula G.; Mouchlis, Varnavas D.; Barbayianni, Efrosini; Kokotos, George; Dennis, Edward A.; Constantinou-Kokotou, Violetta
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 3(2017)
• Page Start: 926
• Page End: 940
• Publication Date: 2017-02-01
• Subjects: Dipeptides -- Inhibitors -- Oxoamides -- Phospholipase A2 -- Pseudodipeptides; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.12.007
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Calcium-independent phospholipase A2 (GVIA iPLA2 ) has recently attracted interest as a medicinal target. The number of known GVIA iPLA2 inhibitors is limited to a handful of synthetic compounds (bromoenol lactone and polyfluoroketones). To expand the chemical diversity, a variety of 2-oxoamides based on dipeptides and ether dipeptides were synthesized and studied for their in vitro inhibitory activity on human GVIA iPLA2 and their selectivity over the other major intracellular GIVA cPLA2 and the secreted GV sPLA2 . Structure-activity relationship studies revealed the first 2-oxoamide derivative (GK317), which presents potent inhibition of GVIA iPLA2 ( X I (50) value of 0.007) and at the same time significant selectivity over GIVA cPLA2 and GV sPLA2 .