A biophysical approach to phospholipase A2 activity and inhibition by anti-inflammatory drugs

The present study describes the interaction of two nonsteroidal anti-inflammatory drugs (ibuprofen and piroxicam) with PLA2 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 PLA2. 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 PLA2 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.

Graphical AbstractResearch Highlights► Piroxicam and ibuprofen are able to inhibit sPLA2 from Naja mossambica mossambica. ► Piroxicam and ibuprofen prevent the enzyme from binding to its lipid substrate, either by shielding the tryptophan residue(s) and limiting the access to the active site, or causing a conformational change of PLA2 structure reducing its ability for catalysis. ► Ibuprofen has been shown to be better stabilized in the lipid layer affecting the performance of sPLA2 and being as a result a stronger inhibitor of its activity.