title: A biophysical approach to phospholipase A2 activity and inhibition by anti-inflammatory drugs.
abstract: The present study describes the interaction of two nonsteroidal anti-inflammatory drugs (ibuprofen and piroxicam) with PLA(2) from Naja mossambica mossambica and seeks to deepen the knowledge about the influence of the biophysical properties of biomembranes, and the inhibitory effect of the drugs on the enzymatic activity. Fluorescent techniques with and without the use of probes, surface pressure/molecular area isotherms, surface pressure/time and molecular area/time measurements combined with circular dichroism spectroscopy and direct techniques of visualization of lipid membranes (Brewster angle microscopy), revealed that both drugs inhibit PLA(2). Additionally, the structure and characteristics of the lipid bilayer, as well as, the direct interaction of drugs with the enzyme seem to play an important role on the hydrolytic activity of PLA(2) towards membrane model systems. These results open a way of finding new and better strategies that can contribute to the development of suitable agents for relieving inflammatory conditions.
authors.affiliation: REQUIMTE, Departamento de Química, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha 164, 4090-030 Porto, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Gaspar
authors.forename: Marlene
authors.initials: M
authors.lastname: Lúcio
authors.forename: Kerstin
authors.initials: K
authors.lastname: Wagner
authors.forename: Gerald
authors.initials: G
authors.lastname: Brezesinski
authors.forename: Sandra
authors.initials: S
authors.lastname: Rocha
authors.forename: J L F
authors.initials: JL
authors.lastname: Costa Lima
authors.forename: Salette
authors.initials: S
authors.lastname: Reis
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology; D055162:Biocatalysis; D020134:Catalytic Domain; D002942:Circular Dichroism; D005456:Fluorescent Dyes / Q000737:chemistry; D007052:Ibuprofen / Q000737:chemistry / Q000494:pharmacology; D008051:Lipid Bilayers / Q000737:chemistry; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000378:metabolism; D010894:Piroxicam / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D064801:Phospholipase A2 Inhibitors; D010894:Piroxicam; D054467:Phospholipases A2; D007052:Ibuprofen