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).