title: Synthesis and antiproliferative activity of 8-hydroxyquinoline derivatives containing a 1,2,3-triazole moiety.
abstract: Twelve novel 8-hydroxyquinoline derivatives were synthesized with good yields by performing copper-catalyzed Huisgen 1,3-dipolar cycloaddition ("click" reaction) between an 8-O-alkylated-quinoline containing a terminal alkyne and various aromatic or protected sugar azides. These compounds were evaluated in vitro for their antiproliferative activity on various cancer cell types. Protected sugar derivative 16 was the most active compound in the series, exhibiting potent antiproliferative activity and high selectivity toward ovarian cancer cells (OVCAR-03, GI50 < 0.25 μg mL(-1)); this derivative was more active than the reference drug doxorubicin (OVCAR-03, GI50 = 0.43 μg mL(-1)). In structure-activity relationship (SAR) studies, the physico-chemical parameters of the compounds were evaluated and docking calculations were performed for the α-glucosidase active site to predict the possible mechanism of action of this series of compounds.
authors: Laboratório de Síntese Orgânica (Labsinto), Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors: Luiza B de O
authors: LB
authors: Freitas
authors: Laboratório de Síntese Orgânica (Labsinto), Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors: Thiago F
authors: TF
authors: Borgati
authors: Laboratório de Síntese Orgânica (Labsinto), Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil.
authors: Rossimiriam P
authors: RP
authors: de Freitas
authors: Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, Campinas, CP 6171, SP 13083-970, Brazil.
authors: Ana L T G
authors: AL
authors: Ruiz
authors: Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, Campinas, CP 6171, SP 13083-970, Brazil.
authors: Gabriela M
authors: GM
authors: Marchetti
authors: Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, Campinas, CP 6171, SP 13083-970, Brazil.
authors: João E
authors: JE
authors: de Carvalho
authors: Laboratório de Química Computacional, Departamento de Química, Universidade Federal de Lavras, CP 3037, Lavras, MG 37200-000, Brazil.
authors: Elaine F F
authors: EF
authors: da Cunha
authors: Laboratório de Química Computacional, Departamento de Química, Universidade Federal de Lavras, CP 3037, Lavras, MG 37200-000, Brazil.
authors: Teodorico C
authors: TC
authors: Ramalho
authors: Laboratório de Síntese Orgânica (Labsinto), Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil. Electronic address: rosebrondi@yahoo.com.br.
authors: Rosemeire B
authors: RB
authors: Alves
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D015125:Oxyquinoline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D014230:Triazoles; D015125:Oxyquinoline
keywords: 1,2,3-Triazole; 8-Hydroxyquinoline; Antiproliferative; “Click” reaction