title: Improvement of the antihypertensive capacity of candesartan and trityl candesartan by their SOD mimetic copper(II) complexes.
abstract: 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 show a 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 stability measurements show that the compounds are stable in ethanolic solutions at least for 1h, while the preservation of the overall stochiometry for both species in solution has been determined by spectrophotometric titrations. By metal 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 human mesangial 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 new insight into the development of copper(II) complexes as potential drugs.
authors.affiliation: Centro de Química Inorgánica (CEQUINOR/CONICET/UNLP)-Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 esq 115, 1900 La Plata, Argentina.
authors.forename: María S
authors.initials: MS
authors.lastname: Islas
authors.forename: Teófilo
authors.initials: T
authors.lastname: Rojo
authors.forename: Luis
authors.initials: L
authors.lastname: Lezama
authors.forename: Mercedes Griera
authors.initials: MG
authors.lastname: Merino
authors.forename: María A
authors.initials: MA
authors.lastname: Cortes
authors.forename: Manuel Rodriguez
authors.initials: MR
authors.lastname: Puyol
authors.forename: Evelina G
authors.initials: EG
authors.lastname: Ferrer
authors.forename: Patricia A M
authors.initials: PA
authors.lastname: Williams
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology*; D001713:Biphenyl Compounds; D003300:Copper / Q000737:chemistry*; D006801:Humans; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D017550:Spectroscopy, Fourier Transform Infrared; D013482:Superoxide Dismutase / Q000378:metabolism; D013777:Tetrazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D003300:Copper; D013482:Superoxide Dismutase; C081643:candesartan