Inhibitory activity of IAA and IBA against lipoxygenase: in silico and in vitro validation

Abstract

Inhibition of leukotriene biosynthesis is considered to be one of the potential treatment strategies for controlling inflammation, respiratory diseases and many neurodegenerative disorders. Designing of specific functional inhibitors against Lipoxygenases (LOX) has got considerable attention due to its ability to block leukotriene biosynthesis. Molecular docking analysis of two indole derivatives such as indoleacetic acid (IAA) and indolebutyric acid (IBA) are reported here. Both compounds give glide scores better than that of protocatechuic acid and nitro catechol, the two known LOX inhibitors. From the enzyme kinetic analysis, it was revealed that IAA and IBA inhibit competitively. The IC₅₀ values determined for both IAA and IBA were 42.98 μM and 17.82 μM, respectively. The binding free energy of these compounds was determined using isothermal titration calorimetric assay and was found to be − 6.12 kcal/mol for IAA and − 7.84 kcal/mol for IBA. From the analysis, it can be concluded that both IAA and IBA might be useful as anti-inflammatory agents.

Keywords::

• LOX
• indoleacetic acid
• indolebutyric acid
• ITC
• inducedfit docking

Acknowledgements

The authors gratefully acknowledge the ‘Bioinformatics Infrastructure Facility’ (supported by DBT, Government of India) located at the Department of Biotechnology and Microbiology, Kannur University for providing the computational work. K.V.D. and C.R. thank ICMR for their Senior Research Fellowships.