title: Synthesis of novel quinoline-2-one based chalcones of potential anti-tumor activity.
abstract: Novel quinoline-2-one based chalcones were synthesized from a Claisen-Schmidt condensation by using the couple KOH/1,4-dioxane as reaction medium. A relatively stable aldol was isolated and identified as the intermediate species in the formation of the target chalcones. Nine of the obtained compounds were in vitro screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines. Products 16c, 16d, 16h and 27 exhibited the highest activity, being compound 27 the most active, displaying remarkable activity against 50 human tumor cell lines, thirteen of them with GI(50) values ≤1.0 μM, being the HCT-116 (Colon, GI(50) = 0.131 μM) and LOX IMVI (Melanoma, GI(50) = 0.134 μM) the most sensitive strains. Compound 27 was referred to in vivo acute toxicity and hollow fiber assay by the Biological Evaluation Committee of the NCI. The acute toxicity study indicated that compound 27 was well tolerated intraperitoneally (150 mg/kg/dose) by athymic nude mice. This compound may possibly be used as lead compound for developing new anticancer agents.
authors.affiliation: Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, A.A. 25360 Cali, Colombia. rodrigo.abonia@correounivalle.edu.co
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Abonia
authors.forename: Daniel
authors.initials: D
authors.lastname: Insuasty
authors.forename: Juan
authors.initials: J
authors.lastname: Castillo
authors.forename: Braulio
authors.initials: B
authors.lastname: Insuasty
authors.forename: Jairo
authors.initials: J
authors.lastname: Quiroga
authors.forename: Manuel
authors.initials: M
authors.lastname: Nogueras
authors.forename: Justo
authors.initials: J
authors.lastname: Cobo
mesh_terms: D000098:Acetophenones / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis* / Q000494:pharmacology; D004146:Dioxanes / Q000737:chemistry; D006878:Hydroxides / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D051379:Mice; D008819:Mice, Nude; D017680:Potassium Compounds / Q000737:chemistry; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000098:Acetophenones; D000447:Aldehydes; D000970:Antineoplastic Agents; D047188:Chalcones; D004146:Dioxanes; D006878:Hydroxides; D017680:Potassium Compounds; D011804:Quinolines; C116609:3-hydroxybutanal; C025223:1,4-dioxane; C029943:potassium hydroxide