Antitumoral, antihypertensive, antimicrobial, and antioxidant effects of an octanuclear copper(II)-telmisartan complex with an hydrophobic nanometer hole.
A new Cu(II) complex with the antihypertensive drug telmisartan, [Cu8Tlm16]·24H2O (CuTlm), was synthesized and characterized by elemental analysis and electronic, FTIR, Raman and electron paramagnetic resonance spectroscopy. The crystal structure (at 120 K) was solved by X-ray diffraction methods. The octanuclear complex is a hydrate of but otherwise isostructural to the previously reported [Cu8Tlm16] complex. [Cu8Tlm16]·24H2O crystallizes in the tetragonal P4/ncc space group with a = b = 47.335(1), c = 30.894(3) Å, Z = 4 molecules per unit cell giving a macrocyclic ring with a double helical structure. The Cu(II) ions are in a distorted bipyramidal environment with a somewhat twisted square basis, cis-coordinated at their core N2O2 basis to two carboxylate oxygen and two terminal benzimidazole nitrogen atoms. Cu8Tlm16 has a toroidal-like shape with a hydrophobic nanometer hole, and their crystal packing defines nanochannels that extend along the crystal c-axis. Several biological activities of the complex and the parent ligand were examined in vitro. The antioxidant measurements indicate that the complex behaves as a superoxide dismutase mimic with improved superoxide scavenger power as compared with native sartan. The capacity of telmisartan and its copper complex to expand human mesangial cells (previously contracted by angiotensin II treatment) is similar to each other. The antihypertensive effect of the compounds is attributed to the strongest binding affinity to angiotensin II type 1 receptor and not to the antioxidant effects. The cytotoxic activity of the complex and that of its components was determined against lung cancer cell line A549 and three prostate cancer cell lines (LNCaP, PC-3, and DU 145). The complex displays some inhibitory effect on the A549 line and a high viability decrease on the LNCaP (androgen-sensitive) line. From flow cytometric analysis, an apoptotic mechanism was established for the latter cell line. Telmisartan and CuTlm show antibacterial and antifungal activities in various strains, and CuTlm displays improved activity against the Staphylococcus aureus strain as compared with unbounded copper(II).
Centro de Química Inorgánica (CEQUINOR/CONICET/UNLP)- Facultad de Ciencias Exactas, Universidad Nacional de La Plata , 47 esq. 115, 1900 La Plata, Argentina.
María S
MS
Islas
Juan J
JJ
Martínez Medina
Libertad L
LL
López Tévez
Teófilo
T
Rojo
Luis
L
Lezama
Mercedes
M
Griera Merino
Laura
L
Calleros
María A
MA
Cortes
Manuel
M
Rodriguez Puyol
Gustavo A
GA
Echeverría
Oscar E
OE
Piro
Evelina G
EG
Ferrer
Patricia A M
PA
Williams
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects; D001562:Benzimidazoles / Q000737:chemistry*; D001565:Benzoates / Q000737:chemistry*; D002460:Cell Line; D003300:Copper / Q000737:chemistry*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D049329:Nanostructures; D000077333:Telmisartan
D000900:Anti-Bacterial Agents; D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D001562:Benzimidazoles; D001565:Benzoates; D003300:Copper; D000077333:Telmisartan