title: New chloro,fluorobenzylindole derivatives as integrase strand-transfer inhibitors (INSTIs) and their mode of action.
abstract: The life cycle of HIV-1 requires extensive assistance from the integrase (IN) enzyme which therefore constitutes an attractive therapeutic target for the development of anti-AIDS agents. We herein report the synthesis and biological evaluation of new HIV integrase strand-transfer inhibitors (INSTIs) which proved to be also potent anti-HIV agents. The binding mode of the most representative molecules were also studied by induced-fit docking (IFD). The obtained IFD results were consistent with the mechanism of action proposed for this class of IN inhibitors, that is metal chelating/binding agents.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, I-98168 Messina, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferro
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Barreca
authors.forename: Sara
authors.initials: S
authors.lastname: De Grazia
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D003198:Computer Simulation; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular
chemical_list: D019428:HIV Integrase Inhibitors; D007211:Indoles; D019427:HIV Integrase