Molecular docking studies of ephedrine, eugenol, and their derivatives as arginase inhibitors: Implications in asthma

KrovvidiS.R Sivasai, Suhasini Donthi, Jayasree Ganugapati, Vijayalakshmi Valluri, Ramesh Macha
2018 International Journal of Pharmaceutical Investigation  
Arginine being a common substrate for arginase and nitric oxide synthase (NOS) an imbalance between enzymes could lead to a shift in airway responses. Reports suggest that increased arginase reduces the substrate availability to NOS and attributes to the airway hyperresponsiveness. Hence, inhibition of arginase might enhance the bioavailability of arginine to NOS and generates nitric oxide (NO) a bronchodilator. Molecules from Ephedra and Eugenia caryophyllus are documented for bronchodilator
more » ... operties. However, the mechanism of action of these molecules for enhancing bronchodilation is not well characterized. The objective of the present study is to assess whether these molecules could inhibit the arginase by binding at its active site and helps in bronchodilation using in silco approach. Methods: The crystal structures of the arginase and NOS enzymes were selected from the protein database. The molecules from Ephedra and Eugenia caryophyllus were obtained from Pubchem. Drug likeliness and bioactivity of the molecules were assessed by Molinspiration. The successful molecules were docked with active sites of enzymes using docking software, and the docked complexes were analyzed using Accelrys Discovery Studio. Results: Molecules from Ephedra and Eugenia caryophyllus were able to interact to arginase at the active site whereas away from the active site in case of NOS. The molecules showed differential binding affinities, and some of them had higher binding affinity than substrate arginine. Conclusion: In silico study suggests that molecules of Ephedra and Eugenia were capable of blocking the active site of arginase. We speculate that if these molecules are used as therapeutics, they could inhibit the arginase activity and this might increase arginine availability to NOS to produce NO which acts as bronchodilator. Our study suggests that molecules which bind to active site of arginine and do not affect the active site of NOS might be the potential molecules for arginase associated asthma. How to cite this article: Donthi S, Ganugapati J, Valluri V, Macha R, Sivasai KS. Molecular docking studies of ephedrine, eugenol, and their derivatives as arginase inhibitors: Implications in asthma. Int J Pharma Investig 2018;8:130-7. This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. Donthi, et al.: Molecular docking studies of arginase inhibitors for asthma Abstract
doi:10.4103/jphi.jphi_25_18 fatcat:uoig2g72zbhklb4th2yfpbbap4