title: Synthesis and biological evaluation of novel antiviral agents as protein-protein interaction inhibitors.
abstract: In continuation of our research efforts toward the identification and optimization for novel inhibitors of interaction between human immunodeficiency virus type 1 integrase and cellular cofactor LEDGF/p75, we designed and synthesized a new series of 4-benzylindole derivatives. Most of the title compounds proved to be able to block this protein-protein interaction (PPI), with a percentage ranging from 30% to 90% at 100 µM. The most promising derivative was compound 10b showing IC50 value of 6.41 µM. The main structure-activity relationships (SAR) are discussed and rationalized by docking studies.
authors.affiliation: Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute, Università di Messina , Messina , Italy and.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferro
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Francesca
authors.initials: F
authors.lastname: Morreale
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D019427:HIV Integrase / Q000378:metabolism*; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D060066:Protein Interaction Maps / Q000187:drug effects*; D017434:Protein Structure, Tertiary
chemical_list: D019380:Anti-HIV Agents; D007211:Indoles; D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1