title: Docking studies on a new human immunodeficiency virus integrase-Mg-DNA complex: phenyl ring exploration and synthesis of 1H-benzylindole derivatives through fluorine substitutions.
abstract: A new model of HIV-1 integrase-Mg-DNA complex that is useful for docking experiments has been built. It was used to study the binding mode of integrase strand transfer inhibitor 1 (CHI-1043) and other fluorine analogues. Molecular modeling results prompted us to synthesize the designed derivatives which showed potent enzymatic inhibition at nanomolar concentration, high antiviral activity, and low toxicity. Microwave assisted organic synthesis (MAOS) was employed in several steps of the synthetic pathway, thus reducing reaction times and improving yields.
authors.affiliation: Dipartimento Farmaco-Chimico, Universita di Messina, Viale Annunziata, 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: Nunzio
authors.initials: N
authors.lastname: Iraci
authors.forename: Sara
authors.initials: S
authors.lastname: De Grazia
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: D002460:Cell Line; D004247:DNA / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry*; D008958:Models, Molecular
chemical_list: D019428:HIV Integrase Inhibitors; D007211:Indoles; D005461:Fluorine; D004247:DNA; D019427:HIV Integrase; D008274:Magnesium