title: Interactions of selected indole derivatives with phospholipase A₂: in silico and in vitro analysis.
abstract: Phospholipase A2 (PLA₂) is one of the key enzymes involved in the formation of inflammatory mediators. Inhibition of PLA₂ 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 PLA₂ (ppsPLA2) 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 PLA₂ (hnpsPLA₂) 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 ppsPLA₂. 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.
authors: Department of Biotechnology and Microbiology and Inter-University Centre for Bioscience, Kannur University, Thalassery Campus, Kannur, Palayad 670661, India.
authors: Kalarickal Vijayan
authors: KV
authors: Dileep
authors: Chandran
authors: C
authors: Remya
authors: Ignatius
authors: I
authors: Tintu
authors: Madathilkovilakathu
authors: M
authors: Haridas
authors: Chittalakkottu
authors: C
authors: Sadasivan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D007210:Indoleacetic Acids / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D007700:Kinetics; D062105:Molecular Docking Simulation; D010179:Pancreas / Q000737:chemistry / Q000201:enzymology; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2 / Q000737:chemistry*; D011485:Protein Binding; D013552:Swine; D013816:Thermodynamics
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D007210:Indoleacetic Acids; D007211:Indoles; D007527:Isoenzymes; D064801:Phospholipase A2 Inhibitors; C014612:indolebutyric acid; C030737:indoleacetic acid; D054467:Phospholipases A2