Title: Exploration of cyclooxygenase-1 binding modes of some chiral anti-inflammatory drugs using molecular docking and dynamic simulations

Authors: Meriem Meyar; Samira Feddal; Zohra Bouakouk; Safia Kellou-Tairi

Addresses: USTHB, Laboratory of Theoretical Physico-Chemistry and Computer Chemistry, Faculty of Chemistry, BP 32 El Alia Bab Ezzouar, Algiers, Algeria ' USTHB, Laboratory of Theoretical Physico-Chemistry and Computer Chemistry, Faculty of Chemistry, BP 32 El Alia Bab Ezzouar, Algiers, Algeria ' USTHB, Laboratory of Theoretical Physico-Chemistry and Computer Chemistry, Faculty of Chemistry, BP 32 El Alia Bab Ezzouar, Algiers, Algeria ' USTHB, Laboratory of Theoretical Physico-Chemistry and Computer Chemistry, Faculty of Chemistry, BP 32 El Alia Bab Ezzouar, Algiers, Algeria

Abstract: The profens represent an important class of chiral anti-inflammatory drugs. They are often marketed as racemic mixtures, but one of their enantiomers R or S can be inactive or toxic. With the aim of evaluating the anti-inflammatory activity of each enantiomer, it would be useful to first theoretically predict the enantiomer responsible for this activity. For that, three well known profens: ibuprofen, flurbiprofen, naproxen and some of their derivatives have been selected from the literature and were studied through docking and molecular dynamic (MD) simulations. Analysis of the recognition modes, through interactions with relevant residues of the cyclooxygenase-1(COX-1), can predict and explain which enantiomer is the most active. MD study highlights that water molecules play an important role in ligand-receptor interactions. Also, our combined study showed the preference of the profen's S-enantiomer towards the COX-1 active site in contrast to R-enantiomer.

Keywords: COX-1; profens; chiral NSAIDs; molecular docking; MD simulations; binding modes.

DOI: 10.1504/IJCBDD.2019.101069

International Journal of Computational Biology and Drug Design, 2019 Vol.12 No.3, pp.281 - 301

Received: 29 Mar 2018
Accepted: 05 Sep 2018
Published online: 23 Jul 2019 *

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