title: Experimental and DFT characterization, antioxidant and anticancer activities of a Cu(II)-irbesartan complex: structure-antihypertensive activity relationships in Cu(II)-sartan complexes.
abstract: The coordination compound of the antihypertensive ligand irbesartan (irb) with copper(II) (CuIrb) was synthesized and characterized by FTIR, FT-Raman, UV-visible, reflectance and EPR spectroscopies. Experimental evidence allowed the implementation of structural and vibrational studies by theoretical calculations made in the light of the density functional theory (DFT). This compound was designed to induce structural modifications on the ligand. No antioxidant effects were displayed by both compounds, though CuIrb behaved as a weak 1,1-diphenyl-2-picrylhydrazyl radical (DPPH(·)) scavenger (IC50 = 425 μM). The measurements of the contractile capacity on human mesangial cell lines showed that CuIrb improved the antihypertensive effects of the parent medication. In vitro cell growth inhibition against prostate cancer cell lines (LNCaP and DU 145) was measured for CuIrb, irbesartan and copper(II). These cell lines have been selected since the angiotensin II type 1 (AT1) receptor (that was blocked by the angiotensin receptor blockers, ARB) has been identified in them. The complex exerted anticancer behavior (at 100 μM) improving the activity of the ligand. Flow cytometry determinations were used to determine late apoptotic mechanisms of cell death. Experimental and DFT characterization of an irbesartan copper(II) complex has been performed. The complex exhibits low scavenging activity against DPPH(·) and significant growth inhibition of LNCaP and DU 145 prostate cancer cell lines. Flow cytometry determinations were used to determine late apoptotic mechanisms of cell death. This compound improved the antihypertensive effect of irbesartan. This effect was observed earlier for the mononuclear Cu-candesartan complex, but not in structurally modified sartans forming dinuclear or octanuclear Cu-sartan compounds.
authors: Facultad de Ciencias Exactas, Centro de Química Inorgánica (CEQUINOR/CONICET/UNLP), Universidad Nacional de La Plata, Bv. 120 e/ 60 y 64 Nº1465, 1900, La Plata, Argentina.
authors: María S
authors: MS
authors: Islas
authors: Department of Systems Biology, Physiology Unity, Medicine School, University of Alcalá, Alcalá de Henares, Madrid, Spain.|IRSIN and REDinREN (Instituto de Salud Carlos III), Madrid, Spain.
authors: Alicia
authors: A
authors: Luengo
authors: Facultad de Ciencias Exactas, Centro de Química Inorgánica (CEQUINOR/CONICET/UNLP), Universidad Nacional de La Plata, Bv. 120 e/ 60 y 64 Nº1465, 1900, La Plata, Argentina.
authors: Carlos A
authors: CA
authors: Franca
authors: Department of Systems Biology, Physiology Unity, Medicine School, University of Alcalá, Alcalá de Henares, Madrid, Spain.|IRSIN and REDinREN (Instituto de Salud Carlos III), Madrid, Spain.
authors: Mercedes Griera
authors: MG
authors: Merino
authors: Department of Systems Biology, Physiology Unity, Medicine School, University of Alcalá, Alcalá de Henares, Madrid, Spain.|IRSIN and REDinREN (Instituto de Salud Carlos III), Madrid, Spain.
authors: Laura
authors: L
authors: Calleros
authors: Department of Systems Biology, Physiology Unity, Medicine School, University of Alcalá, Alcalá de Henares, Madrid, Spain.|IRSIN and REDinREN (Instituto de Salud Carlos III), Madrid, Spain.
authors: Manuel
authors: M
authors: Rodriguez-Puyol
authors: Departamento de Química Inorgánica, Facultad de Ciencia y Tecnología, Universidad del País Vasco, Apdo. 644, 48080, Bilbao, Spain.
authors: Luis
authors: L
authors: Lezama
authors: Facultad de Ciencias Exactas, Centro de Química Inorgánica (CEQUINOR/CONICET/UNLP), Universidad Nacional de La Plata, Bv. 120 e/ 60 y 64 Nº1465, 1900, La Plata, Argentina.
authors: Evelina G
authors: EG
authors: Ferrer
authors: Facultad de Ciencias Exactas, Centro de Química Inorgánica (CEQUINOR/CONICET/UNLP), Universidad Nacional de La Plata, Bv. 120 e/ 60 y 64 Nº1465, 1900, La Plata, Argentina. williams@quimica.unlp.edu.ar.
authors: Patricia A M
authors: PA
authors: Williams
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000737:chemistry*; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry*; D006801:Humans; D000077405:Irbesartan; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D011789:Quantum Theory; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry*
chemical_list: D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D009942:Organometallic Compounds; D013777:Tetrazoles; D003300:Copper; D000077405:Irbesartan
keywords: Antihypertensive; Antioxidant; Copper(II) complex; Cytotoxicity; Irbesartan