title: Synthesis, antiproliferative activities, and computational evaluation of novel isocoumarin and 3,4-dihydroisocoumarin derivatives.
abstract: A series of novel isocoumarin derivatives were synthesized using Castro-Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different tumor cells. Furthermore, docking calculations were performed for the kallikrein 5 (KLK5) active site to predict the possible mechanism of action of this series of compounds. Theoretical findings indicate that the 3,4-dihydroisocoumarin derivative 10a forms hydrogen bonds with Ser190 and Gln192 residues of KLK5. This derivative was the most active compound in the series with potent antiproliferative activity and high selectivity index (SI > 378.79) against breast cancer cells (MCF-7, GI50 = 0.66 μg mL(-1)). This compound represents a promising matrix for developing new antiproliferative agents.
authors: Laboratório de Síntese Orgânica (Labsinto), Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
authors: Keller G
authors: KG
authors: Guimarães
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, SP, CP 6171, 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, SP, CP 6171, 13083-970, Brazil.
authors: Giovanna F
authors: GF
authors: Fiorito
authors: Divisão de Farmacologia e Toxicologia, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, Campinas, SP, CP 6171, 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, 37200-000, Lavras, MG, Brazil.
authors: Elaine F F
authors: EF
authors: da Cunha
authors: Laboratório de Química Computacional, Departamento de Química, Universidade Federal de Lavras, CP 3037, 37200-000, Lavras, MG, 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; D049934:Isocoumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D049934:Isocoumarins
keywords: 3,4-Dihydroisocoumarin; Antiproliferative; Castro–Stephens reaction; Isocoumarin