1 research outputs found
Liposomal Binuclear Ir(III)鈥揅u(II) Coordination Compounds with Phosphino-Fluoroquinolone Conjugates for Human Prostate Carcinoma Treatment
Novel heteronuclear IrIII鈥揅uII coordination
compounds ([Ir(畏5-Cp*)Cl2Pcfx-Cu(phen)](NO3)路1.75(CH3OH)路0.75(H2O) (1), [Ir(畏5-Cp*)Cl2Pnfx-Cu(phen)](NO3)路1.75(CH3OH)路0.75(H2O) (2), [Ir(畏5-Cp*)Cl2Plfx-Cu(phen)](NO3)路1.3(H2O)路1.95(CH3OH) (3), [Ir(畏5-Cp*)Cl2Psfx-Cu(phen)]
(4)) bearing phosphines derived from fluoroquinolones,
namely, sparfloxacin (Hsfx), ciprofloxacin (Hcfx), lomefloxacin (Hlfx),
and norfloxacin (Hnfx), have been synthesized and studied as possible
anticancer chemotherapeutics. All compounds have been characterized
by electrospray ionization mass spectrometry (ESI-MS), a number of
spectroscopic methods (i.e., IR,
fluorescence, and electron paramagnetic resonance (EPR)), cyclic voltammetry,
variable-temperature magnetic susceptibility measurements, and X-ray
diffractometry. The coordination geometry of IrIII in all
complexes adopts a characteristic piano-stool geometry with the 畏5-coordinated and three additional sites occupied by two chloride
and phosphine ligands, while CuII ions in complexes 1 and 2 form a distorted square-pyramidal coordination
geometry, and in complex 3, the coordination geometry
around CuII ions is a distorted octahedron. Interestingly,
the crystal structure of [Ir(畏5-Cp*)Cl2Plfx-Cu(phen)] features the one-dimensional (1D) metal鈥搊rganic
polymer. Liposomes loaded with redox-active and fluorescent [Ir(畏5-Cp*)Cl2Pcfx-Cu(phen)] (1L) have been
prepared to increase water solubility and minimize serious systemic
side effects. It has been proven, by confocal microscopy and an inductively
coupled plasma mass spectrometry (ICP-MS) analysis, that the liposomal
form of compound 1 can be effectively accumulated inside
human lung adenocarcinoma and human prostate carcinoma cells with
selective localization in nuclei. A cytometric analysis showed dominance
of apoptosis over the other cell death types. Furthermore, the investigated
nanoformulations induced changes in the cell cycle, leading to S phase
arrest in a dose-dependent manner. Importantly, in vitro anticancer action on three-dimensional (3D) multicellular tumor
spheroids has been demonstrated