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...

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Bibliographic Details
Published in:Journal of molecular modeling 2013-04, Vol.19 (4), p.1811-1817
Main Authors: Dileep, Kalarickal Vijayan, Remya, Chandran, Tintu, Ignatius, Haridas, Madathilkovilakathu, Sadasivan, Chittalakkottu
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents - chemistry
Binding Sites
Characterization and Evaluation of Materials
Chemistry
Chemistry and Materials Science
Computer Appl. in Life Sciences
Computer Applications in Chemistry
Enzyme Inhibitors - chemistry
Humans
Indoleacetic Acids - chemistry
Indoles - chemistry
Isoenzymes - antagonists & inhibitors
Isoenzymes - chemistry
Kinetics
Molecular Docking Simulation
Molecular Medicine
Original Paper
Pancreas - chemistry
Pancreas - enzymology
Phospholipase A2 Inhibitors
Phospholipases A2 - chemistry
Protein Binding
Swine
Theoretical and Computational Chemistry
Thermodynamics
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Summary: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. Figure Inhibitory activity of IAA and IBA against PLA 2
ISSN:1610-2940
0948-5023
DOI:10.1007/s00894-012-1741-4