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

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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.

Inhibitory activity of IAA and IBA against PLA2

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Acknowledgments

The authors gratefully acknowledge the ‘Bioinformatics Infrastructure Facility’ (supported by DBT, Govt. of India) located at the department of Biotechnology and Microbiology, Kannur University for providing the computational work. K.V.D. thanks for Indian Council of Medical Research (ICMR) for the Senior Research Fellowship.

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Authors and Affiliations

  1. Department of Biotechnology and Microbiology and Inter-University Centre for Bioscience, Kannur University, Thalassery Campus, Kannur, Palayad, 670661, India

    Kalarickal Vijayan Dileep, Chandran Remya, Ignatius Tintu, Madathilkovilakathu Haridas & Chittalakkottu Sadasivan

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  1. Kalarickal Vijayan Dileep
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  2. Chandran Remya
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  3. Ignatius Tintu
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  4. Madathilkovilakathu Haridas
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  5. Chittalakkottu Sadasivan
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Correspondence to Chittalakkottu Sadasivan.

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Dileep, K.V., Remya, C., Tintu, I. et al. Interactions of selected indole derivatives with phospholipase A2: in silico and in vitro analysis. J Mol Model 19, 1811–1817 (2013). https://doi.org/10.1007/s00894-012-1741-4

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  • DOI: https://doi.org/10.1007/s00894-012-1741-4

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