Title

Agemone mexicana flavanones; apposite inverse agonists of the β2-adrenergic receptor in asthma treatment

Authors

Gabriel O. Eniafe^1*, Damilohun S. Metibemu^1,2, Olaposi I. Omotuyi^1,2, Adewale J. Ogunleye¹, Olumide K. Inyang¹, Niyi S. Adelakun¹, Yakubu O. Adeniran², Bamidele Adewumi¹, Ojochenemi A. Enejoh¹, Joseph O. Osunmuyiwa¹, Sidiqat A. Shodehinde², Oluwatoba E. Oyeneyin³

Affiliation

¹Centre for Biocomputing and Drug Development, Adekunle Ajasin University, Akungba Akoko, Ondo State, Nigeria;

²Department of Biochemistry, Adekunle Ajasin University, Akungba Akoko, Ondo State, Nigeria;

³Department of Chemical Sciences, Adekunle Ajasin University, Akungba Akoko, Ondo State, Nigeria;

Email

110401041@aaua.edu.ng;

Article Type

Hypothesis

Date

Received December 18, 2017; Revised January 22, 2018; Accepted January 22, 2018; Published February 28, 2018

Asthma is an inflammatory disease of the airway that poses a major threat to human health. With increase industrialization in the developed and developing countries, the incidence of asthma is on the rise. The β2-adrenergic receptor is an important target in designing anti-asthmatic drugs. The synthetic agonists of the β2-adrenergic receptor used over the years proved effective, but with indispensable side effects, thereby limiting their therapeutic use on a long-term scale. Inverse agonists of this receptor, although initially contraindicated, had been reported to have long-term beneficial effects. Phytochemicals from Agemone mexicana were screened against the human β2-adrenergic receptor in the agonist, inverse agonist, covalent agonist, and the antagonist conformations. Molecular docking of the phyto-constituents showed that the plant constituents bind better to the inverse agonist bound conformation of the protein, and revealed two flavanones; eriodictyol and hesperitin, with lower free energy (ΔG) values and higher affinities to the inverse agonist bound receptor than the co-crystallized ligand. Eriodictyol and hesperitin bind with the glide score of -10.684 and -9.958 kcal/mol respectively, while the standard compound ICI-118551, binds with glide score of -9.503 kcal/mol. Further interaction profiling at the protein orthosteric site and ADME/Tox screening confirmed the drug-like properties of these compounds.

Keywords

Asthma, β2- adrenergic receptor, Inverse agonists, Flavanone.

Citation

Eniafe et al. Bioinformation 14(2): 60-67 (2018)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.