Improvement of the antihypertensive capacity of Candesartan and Trityl candesartan by their SOD mimetic copper(II) complexes

MARÍA S. ISLAS; TEÓFILO ROJO; LUIS LEZAMA; MERCEDES GRIERA MERINO; MARÍA A. CORTÉZ; MANUEL RODRIGUEZ PUYOL; EVELINA G. FERRER; PATRICIA A.M. WILLIAMS

JOURNAL OF INORGANIC BIOCHEMISTRY

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2013 vol. 123 p. 23 - 33

0162-0134

Factor de impacto (2012): 3,197 / Journal Ranking: Q1. Two new complexes [Cu(Cand)(H2O)4] [1] and [Cu2(TCand)4(H2O)2]·4H2O [2] (Cand=candesartan; TCand=trityl candesartan) have been synthesized and thoroughly characterized. The FTIR, Raman, EPR and diffuse reflectance spectra of the solid compounds showa dimeric complex for [2] with carboxylate bridging of the type found in copper(II) acetate. Both elemental analysis and thermal measurements allow the determination of the total stoichiometries of both complexes. The stabilitymeasurements showthat the compounds are stable in ethanolic solutions at least for 1 h,while the preservation of the overall stochiometry for both species in solution has been determined by spectrophotometric titrations. Bymetal complexation the absence of antioxidant behavior of both sartans has been improved. Complexes [1] and [2] are strong superoxidedismutase mimetic compounds and complex [2] also behaves as a peroxyl radical scavenger. Furthermore, this higher antioxidant activity works in parallel with the improvement of the expansive activity over the angiotensin II-induced contracted humanmesangial cells. These new complexes exhibit even higher efficiency as drugs in comparison with the free non-complexed medication with increased antioxidant ability expressing higher capacity to block the angiotensin II contractile effect. This study provides a newinsight into the development of copper(II) complexes as potential drugs. © 2013 Elsevier Inc. All rights reserved.