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.
