title: Oxoquinoline acyclonucleoside phosphonate analogues as a new class of specific inhibitors of human immunodeficiency virus type 1.
abstract: The emergence of a multidrug-resistant HIV-1 strain and the toxicity of anti-HIV-1 compounds approved for clinical use are the most significant problems facing antiretroviral therapies. Therefore, it is crucial to find new agents to overcome these issues. In this study, we synthesized a series of new oxoquinoline acyclonucleoside phosphonate analogues (ethyl 1-[(diisopropoxyphosphoryl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylates 3a-3k), which contained different substituents at the C6 or C7 positions of the oxoquinoline nucleus and an N1-bonded phosphonate group. We subsequently investigated these compounds' in vitro inhibitory effects against HIV-1-infected peripheral blood mononuclear cells (PBMCs). The most active compounds were the fluoro-substituted derivatives 3f and 3g, which presented excellent EC(50) values of 0.4±0.2 μM (3f) and 0.2±0.005 μM (3g) and selectivity index values (SI) of 6240 and 14675, respectively.
authors: Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Outeiro de São João Batista s/n, centro, Niterói, Rio de Janeiro, Brazil.
authors: Letícia V
authors: LV
authors: Faro
authors: Jéssica M
authors: JM
authors: de Almeida
authors: Cláudio C
authors: CC
authors: Cirne-Santos
authors: Viveca A
authors: VA
authors: Giongo
authors: Luís R
authors: LR
authors: Castello-Branco
authors: Ingrid de B
authors: Ide B
authors: Oliveira
authors: Juliana E F
authors: JE
authors: Barbosa
authors: Anna C
authors: AC
authors: Cunha
authors: Vítor F
authors: VF
authors: Ferreira
authors: Marcos C
authors: MC
authors: de Souza
authors: Izabel C N P
authors: IC
authors: Paixão
authors: Maria Cecília B V
authors: MC
authors: de Souza
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009705:Nucleosides / Q000737:chemistry*; D010757:Phosphorous Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D015363:Quinolones / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides; D010757:Phosphorous Acids; D015363:Quinolones