title: The application of rational design on phospholipase A(2) inhibitors.
abstract: The phospholipase A(2) (PLA(2)) superfamily consists of different groups of enzymes which are characterized by their ability to catalyze the hydrolysis of the sn-2 ester bond in a variety of phospholipid molecules. The products of PLA(2s) activity play divergent roles in a variety of physiological processes. There are four main types of PLA(2s): the secreted PLA(2s) (sPLA(2s)), the cytosolic PLA(2s) (cPLA(2s)), the calcium-independent PLA(2s) (iPLA(2)) and the lipoprotein-associated PLA(2s) (LpPLA(2s)). Various potent and selective PLA2 inhibitors have been reported up to date and have provided outstanding support in understanding the mechanism of action and elucidating the function of these enzymes. The current review focuses on the implementation of rational design through computer-aided drug design (CADD) on the discovery and development of new PLA(2) inhibitors.
authors.affiliation: Laboratory of Organic Chemistry, Department of Chemistry, University of Athens, Panepistimiopolis, Athens 15771, Greece.
authors.forename: V D
authors.initials: VD
authors.lastname: Mouchlis
authors.forename: E
authors.initials: E
authors.lastname: Barbayianni
authors.forename: T M
authors.initials: TM
authors.lastname: Mavromoustakos
authors.forename: G
authors.initials: G
authors.lastname: Kokotos
mesh_terms: D001514:Bee Venoms / Q000201:enzymology; D001559:Benzhydryl Compounds / Q000737:chemistry; D020134:Catalytic Domain; D002839:Chromans / Q000737:chemistry; D017076:Computer-Aided Design; D054659:Diketopiperazines / Q000737:chemistry; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors; D006801:Humans; D007211:Indoles / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D010636:Phenols / Q000737:chemistry; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D012717:Sesquiterpenes / Q000737:chemistry; D013449:Sulfonamides / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D001514:Bee Venoms; D001559:Benzhydryl Compounds; D002839:Chromans; D054659:Diketopiperazines; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007211:Indoles; D010636:Phenols; D064801:Phospholipase A2 Inhibitors; D012717:Sesquiterpenes; D013449:Sulfonamides; C500927:bolinaquinone; C084181:YM 26734; C086203:FPL 67047XX; D005680:gamma-Aminobutyric Acid; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human; D054467:Phospholipases A2