RESUMEN
In the present study, a series of 13-β-elemene ester derivatives were designed and prepared, and their antioxidant activity was investigated in the H2O2-treated human umbilical vein endothelial cells (HUVECs). Among the test compounds, the dimer compounds 5v and 5w exhibited the most potent antioxidant activity with significant ROS suppression being observed. Both compounds markedly inhibited the H2O2-induced changes in various biochemical substances, such as superoxide dismutase (SOD), malonyldialdehyde (MDA), nitric oxide (NO), and lactic dehydrogenase (LDH), which were superior to that of the positive control vitamin E. Further more, they did not produce any obvious cytotoxicity, but increased the viability of HUVECs injured by H2O2 in a dose-dependent manner. Additionally, compound 5w, designed as a prodrug-like compound, showed improved stability relative to compound 4 in vitro.
Asunto(s)
Humanos , Antioxidantes , Metabolismo , Farmacología , Células Cultivadas , Curcuma , Química , Estabilidad de Medicamentos , Medicamentos Herbarios Chinos , Química , Farmacología , Endotelio Vascular , Biología Celular , Metabolismo , Células Endoteliales de la Vena Umbilical Humana , Peróxido de Hidrógeno , Metabolismo , Malondialdehído , Metabolismo , Óxido Nítrico , Metabolismo , Oxidación-Reducción , Estrés Oxidativo , Ácidos Ftálicos , Farmacología , Sesquiterpenos , Farmacología , Succinatos , Farmacología , Superóxido Dismutasa , MetabolismoRESUMEN
AIM@#In a search for new cardiovascular drug candidates, a series of novel oxime ethers derived from a natural isochroman-4-one were synthesized.@*METHOD@#Compounds 3 and 6, derived from the natural antihypertensive compound 7, 8-dihydroxy-3-methyl-isochroman-4-one (XJP), were designed and synthesized. Subsequently, a series of novel isochroman-4-one oxime ether hybrids were prepared by hybridizing various N-substituted isopropanolamine functionalities to isochroman-4-one oxime. Furthermore, β1-adrenergic blocking activities of the synthesized compounds were assayed using the isolated rat left atria.@*RESULTS@#Twenty target compounds were obtained, and the preliminary structure-activity relationships were deduced. The most promising compound Ic exhibited β1-adrenoceptor blocking activity (inhibition: 52.2%) at 10(-7) mol·L(-1), which was superior to that of propranolol (inhibition: 49.7%).@*CONCLUSION@#The results suggested that natural product XJP/isopropanolamine moiety hybrids may provide a promising approach for the discovery of novel cardiovascular drug candidates.
Asunto(s)
Animales , Humanos , Masculino , Ratas , Antagonistas Adrenérgicos beta , Química , Farmacología , Antihipertensivos , Química , Farmacología , Benzopiranos , Química , Farmacología , Medicamentos Herbarios Chinos , Química , Farmacología , Hipertensión , Quimioterapia , Estructura Molecular , Oximas , Química , Ratas Sprague-Dawley , Relación Estructura-ActividadRESUMEN
A practical approach to the synthesis of the A, B and C-ring subunit of cyclopamine has been developed. This synthetic tactic highlights the utility of mandelate acetal-mediated resolution of the fused ring ketone (±)-4 and IBX-mediated oxidation cascades from 12 to 9. The availability of advanced intermediates from enantiomerically pure (+)-4 and 2 could provide efficient access to biologically active and structurally diverse C-nor-D-homo-steroidal alkaloids such as cyclopamine.