title: Docking and Molecular Dynamics Calculations of Pyrrolidinone Analog MMK16 Bound to COX and LOX Enzymes.
abstract: The new molecule 4-[(2S)-2-(1H-imidazol-1-ylmethyl)-5-oxotetrahydro-1H-pyrrol-1-yl]methylbenzenecarboxylic acid (MMK16) was found to have promising anti-inflammatory activity. This biological behavior of MMK16 triggered our interest to study its binding affinity using NMR spectroscopy in LOX and its docking and molecular dynamics (MD) properties in LOX and COX enzymes. The present NMR and docking binding studies not only rationalize the obtained biological results since in all three receptors MMK16 shows high affinity and scoring but also make it a potential dual LOX-5/COX-2 inhibitor. Thus, this class of molecules must be further investigated for discovering compounds possessing better biological activity and more lasting biological effect.
authors.affiliation: Kapodistrian University of Athens, Panepistimiopolis, Zographou 15784, Athens, Greece.|Authors contributed equally to this work.
authors.forename: N
authors.initials: N
authors.lastname: Neophytou
authors.affiliation: National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, Vas. Constantinou 48, 11635 Athens, Greece. gleonis@eie.gr.|Authors contributed equally to this work. gleonis@eie.gr.
authors.forename: G
authors.initials: G
authors.lastname: Leonis
authors.affiliation: Kapodistrian University of Athens, Panepistimiopolis, Zographou 15784, Athens, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Stavrinoudakis
authors.affiliation: Laboratory of Biomolecular Structure, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.|EN-FIST Centre of Excellence, Dunajska 156, SI-1000 Ljubljana, Slovenia.
authors.forename: M
authors.initials: M
authors.lastname: Simčič
authors.affiliation: Laboratory of Biomolecular Structure, National Institute of Chemistry, Hajdrihova 19, SI-1001 Ljubljana, Slovenia.|EN-FIST Centre of Excellence, Dunajska 156, SI-1000 Ljubljana, Slovenia.
authors.forename: S Golič
authors.initials: SG
authors.lastname: Grdadolnik
authors.affiliation: Kapodistrian University of Athens, Panepistimiopolis, Zographou 15784, Athens, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Papavassilopoulou
authors.affiliation: Kapodistrian University of Athens, Panepistimiopolis, Zographou 15784, Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Michas
authors.affiliation: Kapodistrian University of Athens, Panepistimiopolis, Zographou 15784, Athens, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Moutevelis-Minakakis
authors.affiliation: National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, Vas. Constantinou 48, 11635 Athens, Greece.
authors.forename: M G
authors.initials: MG
authors.lastname: Papadopoulos
authors.affiliation: Drug Discovery and Design Center (DDDC), Box 1201, Shanghai Institute of Materia Medica No. 555 Rd. Zuchongzhi, Shanghai, P. R. China.
authors.forename: M
authors.initials: M
authors.lastname: Zing
authors.affiliation: Kapodistrian University of Athens, Panepistimiopolis, Zographou 15784, Athens, Greece. tmavrom@chem.uoa.gr.
authors.forename: T
authors.initials: T
authors.lastname: Mavromoustakos
keywords: COX; Drug design; LOX; Molecular dynamics; Pyrrolidinone analogs