title: Indolyl aryl sulphones as HIV-1 non-nucleoside reverse transcriptase inhibitors: synthesis, biological evaluation and binding mode studies of new derivatives at indole-2-carboxamide.
abstract: New non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are active against the commonly occurring mutations of HIV are urgently needed for the treatment of AIDS. We synthesized new NNRTIs of the indolyl aryl sulphone (IAS) family, which are endowed with high antiviral potency against HIV-1 wt (wild-type), and the Y181C and K103N-Y181C drug resistant mutant strains. Several new compounds were highly active in lymphocytes infected with primary isolates carrying the K103N-V1081-M184V and L1001-V1081 mutations. The design of new IASs was based on three-dimensional quantitative structure-activity relationship (3D QSAR) studies and docking simulations. A cross-docking study was also undertaken to gain some insights in to the binding mode of the newly synthesized IASs in the wt and mutated isoforms of reverse transcriptase.
authors.affiliation: Istituto Pasteur Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Università di Roma 'La Sapienza', Roma, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: De Martino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Regina
authors.forename: Rino
authors.initials: R
authors.lastname: Ragno
authors.forename: Antonio
authors.initials: A
authors.lastname: Coluccia
authors.forename: Alberto
authors.initials: A
authors.lastname: Bergamini
authors.forename: Chiara
authors.initials: C
authors.lastname: Ciaprini
authors.forename: Anna
authors.initials: A
authors.lastname: Sinistro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
authors.forename: Emmanuele
authors.initials: E
authors.lastname: Crespan
authors.forename: Marino
authors.initials: M
authors.lastname: Artico
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
mesh_terms: D002460:Cell Line; D006801:Humans; D007211:Indoles / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013450:Sulfones / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D007211:Indoles; D018894:Reverse Transcriptase Inhibitors; D013450:Sulfones