title: Specific targeting of highly conserved residues in the HIV-1 reverse transcriptase primer grip region. 2. Stereoselective interaction to overcome the effects of drug resistant mutations.
abstract: Starting from the prototypic compound 4, we describe new, potent, and broad-spectrum pyrrolobenzo(pyrido)oxazepinones antivirals. A biochemical and enzymological investigation was performed for defining their mechanism of inhibition at either recombinant HIV-1 RT wild type and non-nucleoside reverse transcriptase inhibitors (NNRTIs)-resistant mutants. For the novel compounds (S)-(+)-5 and (S)-(-)-7, a clear-cut stereoselective mechanism of enzyme inhibition was found. Molecular modeling studies were performed for revealing the underpinnings of this behavior.
authors.affiliation: Dipartimento Farmaco Chimico Tecnologico, Universita di Siena, via Aldo Moro 2, 53100 Siena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Butini
authors.forename: Margherita
authors.initials: M
authors.lastname: Brindisi
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Borrelli
authors.forename: Salvatore Sanna
authors.initials: SS
authors.lastname: Coccone
authors.forename: Anna
authors.initials: A
authors.lastname: Ramunno
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Samantha
authors.initials: S
authors.lastname: Zanoli
authors.forename: Alberta
authors.initials: A
authors.lastname: Samuele
authors.forename: Gianluca
authors.initials: G
authors.lastname: Giorgi
authors.forename: Alberto
authors.initials: A
authors.lastname: Bergamini
authors.forename: Michela
authors.initials: M
authors.lastname: Di Mattia
authors.forename: Silvana
authors.initials: S
authors.lastname: Lalli
authors.forename: Bruno
authors.initials: B
authors.lastname: Galletti
authors.forename: Sandra
authors.initials: S
authors.lastname: Gemma
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maga
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology; D017124:Conserved Sequence; D004351:Drug Resistance / Q000187:drug effects* / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase