RESUMEN
Thirty-one 2'-hydroxychalcones were prepared via solid-phase synthesis by base-catalyzed aldol condensation of substituted 2'-hydroxyacetophenones and benzaldehydes. Chalcones were tested for their growth inhibitory activity in three human tumor cell lines (MCF-7, NCI-H460 and A375-C5) using the SRB assay. Results revealed that several of the tested compounds caused a pronounced dose-dependent growth inhibitory effect on the tumor cell lines studied in the low micromolar range. To gain further insight on the cellular mechanism of action of this class of compounds, studies of their effect on cell cycle profile as well as on induction of cellular apoptosis were also carried out. Generally, the tested chalcones interfered with the cell cycle profile and increased the percentage of apoptotic MCF-7 cells. The results here presented may help to identify new chalcone-like structures with optimized cell growth inhibitory activity which may be further tested as potential antitumor agents.
Asunto(s)
Antineoplásicos/síntesis química , Chalconas/química , Antineoplásicos/química , Antineoplásicos/farmacología , Apoptosis , Benzaldehídos/química , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Chalconas/síntesis química , Chalconas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Técnicas de Síntesis en Fase Sólida , Relación Estructura-ActividadRESUMEN
Fourteen baicalein and 3,7-dihydroxyflavone derivatives were synthesized and evaluated for their inhibitory activity against the in vitro growth of three human tumor cell lines. The synthetic approaches were based on the reaction with prenyl or geranyl bromide in alkaline medium, followed by cyclization of the respective monoprenylated derivative. Dihydropyranoflavonoids were also obtained by one-pot synthesis, using Montmorillonite K10 clay as catalyst combined with microwave irradiation. In vitro screening of the compounds for cell growth inhibitory activity revealed that the presence of one geranyl group was associated with a remarkable increase in the inhibitory activity. Moreover, for the 3,7-dihydroxyflavone derivatives a marked increase in growth inhibitory effect was also observed for compounds with furan and pyran fused rings. The most active compounds were also studied regarding their effect on cell cycle profile and induction of apoptosis. Overall the results point to the relevant role of the prenylation of flavone scaffold in the growth inhibitory activity of cancer cells.