title: Rational Design, Synthesis and Evaluation of Coumarin Derivatives as Protein-protein Interaction Inhibitors.
abstract: Herein we describe the design and synthesis of a new series of coumarin derivatives searching for novel HIV-1 integrase (IN) allosteric inhibitors. All new obtained compounds were tested in order to evaluate their ability to inhibit the interaction between the HIV-1 IN enzyme and the nuclear protein lens epithelium growth factor LEDGF/p75. A combined approach of docking and molecular dynamic simulations has been applied to clarify the activity of the new compounds. Specifically, the binding free energies by using the method of molecular mechanics-generalized Born surface area (MM-GBSA) was calculated, whereas hydrogen bond occupancies were monitored throughout simulations methods.
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università degli Studi di Messina, Viale Annunziata, I-98168, Messina, Italy. ldeluca@unime.it.
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università degli Studi di Messina, Viale Annunziata, I-98168, Messina, Italy. fagharbaoui@unime.it.
authors.forename: Fatima E
authors.initials: FE
authors.lastname: Agharbaoui
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università degli Studi di Messina, Viale Annunziata, I-98168, Messina, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università degli Studi di Messina, Viale Annunziata, I-98168, Messina, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Buemi
authors.affiliation: Molecular Virology and Gene Therapy KU Leuven and IRC KULAK, Kapucijnenvoer 33, B-3000, Leuven, Flanders, Belgium.
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.affiliation: Molecular Virology and Gene Therapy KU Leuven and IRC KULAK, Kapucijnenvoer 33, B-3000, Leuven, Flanders, Belgium.
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università degli Studi di Messina, Viale Annunziata, I-98168, Messina, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferro
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry* / Q000494:pharmacology; D055808:Drug Discovery / Q000379:methods; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D062105:Molecular Docking Simulation / Q000379:methods; D056004:Molecular Dynamics Simulation; D011485:Protein Binding / Q000187:drug effects; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects*
chemical_list: D003374:Coumarins; D019428:HIV Integrase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor
keywords: Docking; HIV-1; IN; LEDGF/p75; Molecular Dynamics