title: Pharmacophore-based design of HIV-1 integrase strand-transfer inhibitors.
abstract: Using a training set of diketo-like acid HIV-1 integrase (IN) strand-transfer inhibitors, a 3D pharmacophore model was derived having quantitative predictive ability in terms of activity. The best statistical hypothesis consisted of four features (one hydrophobic aromatic region, two hydrogen-bond acceptors, and one hydrogen-bond donor) with r of 0.96. The resulting pharmacophore model guided the rational design of benzylindoles as new potent IN inhibitors, whose microwave-assisted synthesis and biological evaluation are reported.
authors.affiliation: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, 98168 Messina, Italy. barreca@pharma.unime.it
authors.forename: Maria Letizia
authors.initials: ML
authors.lastname: Barreca
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferro
authors.forename: Angela
authors.initials: A
authors.lastname: Rao
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Maria
authors.initials: M
authors.lastname: Zappalà
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Monforte
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
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; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D015195:Drug Design; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007651:Keto Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D019428:HIV Integrase Inhibitors; D007651:Keto Acids; D019427:HIV Integrase