In Vitro and in Vivo Evaluation of Water-Soluble Iminophosphorane Ruthenium(II) Compounds. A Potential Chemotherapeutic Agent for Triple Negative Breast Cancer

A series
of organometallic ruthenium­(II) complexes containing iminophosphorane
ligands have been synthesized and characterized. Cationic compounds
with chloride as counterion are soluble in water (70–100 mg/mL).
Most compounds (especially highly water-soluble 2) are
more cytotoxic to a number of human cancer cell lines than cisplatin.
Initial mechanistic studies indicate that the cell death type for
these compounds is mainly through canonical or caspase-dependent apoptosis,
nondependent on p53, and that the compounds do not interact with DNA
or inhibit protease cathepsin B. In vivo experiments of 2 on MDA-MB-231 xenografts in NOD.CB17-Prkdc SCID/J mice showed an
impressive tumor reduction (shrinkage) of 56% after 28 days of treatment
(14 doses of 5 mg/kg every other day) with low systemic toxicity.
Pharmacokinetic studies showed a quick absorption of 2 in plasma with preferential accumulation in the breast tumor tissues
when compared to kidney and liver, which may explain its high efficacy
in vivo.