RESUMEN
Overcoming drug resistance with remarkable cytotoxic activity by anthracene-9,10-dione derivatives would offer a potential therapeutic strategy. In this study, we report the synthesis and the cytotoxicity of a novel set of anthraquninones. (4-(4-Aminobenzylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl-4-methylbenzenesulfonate) (3) has excellent in vitro cytotoxicity against doxorubicin-resistant cancer cell line (IC50=0.8 µM), 20-fold higher than doxorubicin. The cytotoxic effect via G2/M arrest does not appear to be ROS.
Asunto(s)
Antraquinonas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Doxorrubicina/farmacología , Antraquinonas/química , Antibióticos Antineoplásicos/farmacología , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Femenino , HumanosRESUMEN
6-Deoxyclitoriacetal (1) and a series of 11 further derivatives of it (2-12) were synthesized and evaluated for their cytotoxic and topoisomerase IIα inhibitory activities. Compounds bearing epoxide (2), morpholine (6) and benzylamine (10) moieties showed promising in vitro cytotoxic activities against four cancer cell lines, with IC(50) values ranging from 0.38 to 0.73 µM. These three compounds also strongly inhibited topoisomerase II activity at 68.3-93.5% and showed a moderately high DNA intercalating property.
Asunto(s)
Antineoplásicos/farmacología , ADN-Topoisomerasas de Tipo II/metabolismo , Inhibidores Enzimáticos/farmacología , Rotenona/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Bovinos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Activación Enzimática/efectos de los fármacos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Estructura Molecular , Rotenona/análogos & derivados , Rotenona/síntesis química , Estereoisomerismo , Relación Estructura-Actividad , TemperaturaRESUMEN
In the title compound, C(22)H(21)ClO(8), the rotenoid core is nearly planar (r.m.s. deviation 0.114â Å), with the largest deviations from the least-squares plane being 0.286â (3) and 0.274â (2)â Å. An inter-molecular O-Hâ¯O hydrogen bond links two mol-ecules into a centrosymmetric dimer having an R(2) (2)(18) ring motif.
RESUMEN
A new series of anthracene-9, 10-dione derivatives have been synthesized to increase cytotoxic activity against human papillomavirus (HPV) positive cancer cell line, CaSki. The highest cytotoxicity was achieved by 4-(benzylamino)-9,10-dioxo-4a,9,9a,10-tetrahydroanthracen-1-yl 4-ethylbenzenesulfonate (5) with the inhibitory concentration 50 (IC50) of 0.3 µM which is 20 times lower than that of cisplatin (CDDP; IC50 = 8.0 µM). The toxicity against non-cancerous cell line, WI-38, was low with the IC50 > 10 µM. Treatment with this compound resulted in decreasing HPV E6 expression. Furthermore, increasing p53 and decreasing Bcl-2 expression were noted. Cell cycle profiles revealed an accumulation of cells in the G2/M phase.