Losartan and its interaction with copper(II): Biological effects

被引:30
作者
Etcheverry, Susana B.
Ferrer, Evelina G.
Naso, Luciana
Barrio, Daniel A.
Lezama, Luis
Rojo, Tefilo
Williams, Patricia A. M. [1 ]
机构
[1] Univ Nacl La Plata, Fac Ciencias Exactas, Ctr Quim Inorgan, La Plata, Argentina
[2] Univ Nacl La Plata, Fac Ciencias Exactas, Catedra Bioquim Patol, La Plata, Argentina
[3] Univ Basque Country, Fac Ciencias & Tecnol, Dept Quim Inorgan, E-48080 Bilbao, Spain
关键词
antiltypertensive; losartan; copper complex; biological activities;
D O I
10.1016/j.bmc.2007.06.056
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Losartan, the potassium salt of 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imi-dazol, 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. (C) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码:6418 / 6424
页数:7
相关论文
共 39 条
[1]   Reinvestigation of the copper(Il)-carcinine equilibrium system: "two-dimensional" EPR simulation and NMR relaxation studies for determining the formation constants and coordination modes [J].
Arkosi, Z ;
Paksi, Z ;
Korecz, L ;
Gajda, T ;
Henry, B ;
Rockenbauer, A .
JOURNAL OF INORGANIC BIOCHEMISTRY, 2004, 98 (12) :1995-2005
[2]  
Beauchamp C., 1971, ANAL BIOCHEM, V44, P276, DOI DOI 10.1016/0003-2697(71)90370-8
[3]  
BENCINI A, 1990, ELECTRON PARAMAGNETI, P167
[4]   STRUCTURE AND SUPEROXIDE-DISMUTASE ACTIVITY OF RU(II), CU(II), AND MN(II) MACROCYCLIC COMPLEXES [J].
BIENVENUE, E ;
CHOUA, S ;
LOBORECIO, MA ;
MARZIN, C ;
PACHECO, P ;
SETA, P ;
TARRAGO, G .
JOURNAL OF INORGANIC BIOCHEMISTRY, 1995, 57 (03) :157-168
[5]   Vibrational spectroscopy of triazoles and tetrazole [J].
Billes, F ;
Endrédi, H ;
Keresztury, G .
JOURNAL OF MOLECULAR STRUCTURE-THEOCHEM, 2000, 530 (1-2) :183-200
[6]   COPPER(II) INTERACTION AND COMPLEXATION WITH 1-[2(S)-3-MERCAPTO-3-METHYLPROPIONYL]-L-PROLINE (CAPTOPRIL) [J].
BONTCHEV, PR ;
GOCHEV, G ;
EVTIMOVA, B ;
KADUM, H ;
NACHEV, C .
JOURNAL OF INORGANIC BIOCHEMISTRY, 1992, 46 (01) :23-34
[7]   Arterial hypertension and stroke prevention: An update [J].
Bornstein, N ;
Silvestrelli, G ;
Caso, V ;
Parnetti, L .
CLINICAL AND EXPERIMENTAL HYPERTENSION, 2006, 28 (3-4) :317-326
[8]   Spondylo-epi-metaphyseal dysplasia (SEMD) matrilin 3 type: homozygote matrilin 3 mutation in a novel form of SEMD [J].
Borochowitz, ZU ;
Scheffer, D ;
Adir, V ;
Dagoneau, N ;
Munnich, A ;
Cormier-Daire, V .
JOURNAL OF MEDICAL GENETICS, 2004, 41 (05) :366-372
[9]   Copper control as an antiangiogenic anticancer therapy: Lessons from treating Wilson's disease [J].
Brewer, GJ .
EXPERIMENTAL BIOLOGY AND MEDICINE, 2001, 226 (07) :665-673
[10]  
Cass A E, 1980, Ciba Found Symp, V79, P71