CONICET | Buscador de Institutos y Recursos Humanos

Radical 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). Measurements of their ability to inhibit the agiotensin II-induced reduction of planar cell surface area were performed. In fact, sartans inhibit the reduction of the area, but the best cellular relaxation was achieved by their SOD mimetic copper(II) compounds.

enviar mensaje