Interactions of selected indole derivatives with phospholipase A2: in silico and in vitro analysis

Phospholipase A2 (PLA(2)) is one of the key enzymes involved in the formation of inflammatory mediators. Inhibition of PLA(2) is considered to be one of the efficient methods to control inflammation. In silico docking studies of 160 selected indole derivatives performed against porcine pancreatic PLA(2) (ppsPLA(2)) suggested that, CID2324681, CID8617 (indolebutyric acid or IBA), CID22097771 and CID802 (indoleacetic acid or IAA) exhibited highest binding energies. In silico analysis was carried out to predict some of the ADME properties. The binding potential of these compounds with human non pancreatic secretory PLA(2) (hnpsPLA(2)) was determined using molecular docking studies. In order to corroborate the in silico results, enzyme kinetics and isothermal titration calorimetric analysis of the two selected compounds, IAA and IBA were performed against ppsPLA(2). From the analysis, it was concluded that IAA and IBA can act as competitive inhibitors to the enzyme and may be used as anti inflammatory agents.