title: New 1H-Benzo[f]indazole-4,9-diones Conjugated with C-Protected Amino Acids and Other Derivatives: Synthesis and in Vitro Antiproliferative Evaluation.
abstract: 1H-Benzo[f]indazole-4,9-dione derivatives conjugated with C-protected amino acids (glycine, l-alanine, l-phenylalanine and l-glutamic acid) 6a-l were prepared by chemically modifying the prenyl substituent of 3-methyl-7-(4-methylpent-3-enyl)-1H-benzo[f]indazole-4,9-dione 2 through epoxidation, degradative oxidation, oxidation and N-acyl condensation reactions. The chemical structures of the synthesized compounds were elucidated by analyzing their IR, ¹H-NMR and (13)C-NMR spectral data together with elemental analysis for carbon, hydrogen and nitrogen. The preliminary in vitro antiproliferative activity of the synthesized derivatives was evaluated on KATO-III and MCF-7 cell lines using a cell proliferation assay. The majority of the derivatives exhibited significant antiproliferative activity with IC50 values ranging from 25.5 to 432.5 μM. These results suggest that 1H-benzo[f]indazole-4,9-dione derivatives are promising molecules to be researched for developing new anticancer agents.
authors.affiliation: Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile. amolinar@ucv.cl.
authors.forename: Aurora
authors.initials: A
authors.lastname: Molinari
authors.affiliation: Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile. aoliva@ucv.cl.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Oliva
authors.affiliation: Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile. m.arismendi.m@gmail.com.
authors.forename: Marlene
authors.initials: M
authors.lastname: Arismendi-Macuer
authors.affiliation: Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile. leda.guzman@ucv.cl.
authors.forename: Leda
authors.initials: L
authors.lastname: Guzmán
authors.affiliation: Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile. mauricio.fuentealba@ucv.cl.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Fuentealba
authors.affiliation: Instituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso 2373223, Chile. marcela.knox@gmail.com.
authors.forename: Marcela
authors.initials: M
authors.lastname: Knox
authors.affiliation: Facultad de Farmacia, Universidad de Valparaíso, Valparaíso 2360102, Chile. raul.vinet@uv.cl.|Centro Regional de Estudios en Alimentos y Salud (CREAS), Valparaíso 2362696, Chile. raul.vinet@uv.cl.
authors.forename: Raúl
authors.initials: R
authors.lastname: Vinet
authors.affiliation: Facultad de Farmacia, Departamento de Química Farmacéutica, CIETUS, IBSAL, Universidad de Salamanca, Salamanca 37007, Spain. asf@usal.es.
authors.forename: Arturo
authors.initials: A
authors.lastname: San Feliciano
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007191:Indazoles / Q000737:chemistry*; D015394:Molecular Structure; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000596:Amino Acids; D000970:Antineoplastic Agents; D007191:Indazoles
keywords: 1,4-naphthoquinone; 1H-benzoindazole; amino acid; pyrazole