CEQUINOR   05415
CENTRO DE QUIMICA INORGANICA "DR. PEDRO J. AYMONINO"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Improvement of the antihypertensive capacity of candesartan and trityl candesartan by their SOD mimetic copper(II) complexes
Autor/es:
ISLAS, MARÍA SOLEDAD; ROJO TEÓFILO; LEZAMA LUIS; CORTES, MARÍA ALICIA; RODRIGUEZ PUYOL, MANUEL ; FERRER , EVELINA; WILLIAMS, PATRICIA A.M.
Lugar:
Granada
Reunión:
Congreso; 11th European Biological Inorganic Chemistry Conference (EUROBIC11); 2012
Institución organizadora:
Universidad de Granada
Resumen:
Improvement of the antihypertensive capacity of candesartan and trityl candesartan by their SOD mimetic copper(II) complexes.Islas, M.S a.; Rojo, T b.; Lezama, L b.; Cortes, M.A c.; Rodriguez Puyol, M c.; Ferrer, E.G a.; Williams, P.A.M a.a Centro de Química Inorgánica (CEQUINOR/CONICET/UNLP)- National University of La Plata. 47 y 115, 1900. La Plata, Argentina. williams@quimica.unlp.edu.arb University of País Vasco, Department of Inorganic Chemistry, Faculty of Science and Technology, Apdo. 644, 48080, Bilbao, Spain.c Departamento de Fisiología, Universidad de Alcalá, Campus Universitario, 28871-Alcalá de Henares, Madrid, SpainRadical scavengers can improve the endogenous vasodilatory effect of NO avoiding its interaction with reactive oxygen species (ROS), specifically superoxide, during hypertension [1]. Moreover, sartans are therapeutically developed angiotensin II receptor antagonists applied in antihypertensive therapies [2]. Once these drugs are administered they are able to interact with bioavailable metal ions such as copper(II) due to the presence of donor atoms (N and O) in their structure. To improve the antihypertensive effect of sartans we have prepared solid coordination Cu(II) complexes with candesartan and tritylcandesartan that can act as superoxidedismutase mimics. The compounds were characterized by means of elemental analysis, thermal decomposition and UV-vis, diffuse reflectance, infrared, Raman and EPR spectroscopies. The stability of these complexes in ethanolic solutions was determined. The free radical scavenging capacities were measured on ABTS.+, DPPH. radicals, and on different ROS hydroxyl and peroxyl radicals and superoxide anion. Candesartan and trityl candesartan did not effectively scavenge free radicals. However, their copper(II) complexes improved some of these activities. [Cu(cand)(H2O)2].2H2O, behaved as a good superoxide anion scavenger (IC50 = 5.5μM) and [Cu2(Tcand)4(H2O)2].4H2O, acted as a mild superoxidedismutase mimic (IC50 = 47.5μM) and a good peroxyl radical scavenger (nearly half of the activity of the reference standard, Trolox).The ability of angiotensin II to reduce the planar cell surface area in human mesangial cells pretreated with same compounds was analysed. In fact, sartans are able to prevent the contraction induced by angiotensin II, but the best cellular relaxation was achieved by their SOD mimetic copper (II) compounds.References[1] M.R. Tschudi, S. Mesaros, T.F. Lüscher, T. Malinski, Hypertension. 1996; 27, 32.[2] C.I. Johnston, Lancet. 1995; 346, 140
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