title: Losartan and its interaction with copper(II): biological effects.
abstract: Losartan, the potassium salt of 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazol, is an efficient antihypertensive drug. The vibrational FTIR and Raman spectra of Losartan (its anionic and protonated forms) are discussed. In addition, the copper(II) complex of Losartan was obtained and characterized as a microcrystalline powder. The metal center is bound to the ligand through the nitrogen atoms of the tetrazolate moiety as determined by vibrational spectroscopy. The compound is a dimer with the metal centers in a tetragonal distorted environment but the presence of a monomeric impurity has been determined by EPR spectroscopy. The antioxidant properties of the complex (superoxide dismutase mimetic activity) and its effect on the proliferation and morphology of two osteoblast-like cells in culture are reported. The new compound exerted more toxic effects on tumoral cells than the copper(II) ion and Losartan.
authors.affiliation: Centro de Química Inorgánica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, 47 y 115 (1900) La Plata, Argentina.
authors.forename: Susana B
authors.initials: SB
authors.lastname: Etcheverry
authors.forename: Evelina G
authors.initials: EG
authors.lastname: Ferrer
authors.forename: Luciana
authors.initials: L
authors.lastname: Naso
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Barrio
authors.forename: Luis
authors.initials: L
authors.lastname: Lezama
authors.forename: Teófilo
authors.initials: T
authors.lastname: Rojo
authors.forename: Patricia A M
authors.initials: PA
authors.lastname: Williams
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001667:Binding, Competitive; D002413:Cations, Divalent; D049109:Cell Proliferation / Q000187:drug effects*; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D004195:Disease Models, Animal; D004578:Electron Spin Resonance Spectroscopy; D008024:Ligands; D019808:Losartan / Q000737:chemistry / Q000378:metabolism*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000378:metabolism; D013777:Tetrazoles / Q000737:chemistry / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000959:Antihypertensive Agents; D000975:Antioxidants; D002413:Cations, Divalent; D008024:Ligands; D013777:Tetrazoles; D003300:Copper; D013482:Superoxide Dismutase; D019808:Losartan