Uses
NAMI-A is a ruthenium-based drug characterised by the selective activity against tumour metastases, inhibits the adhesion and migration.
In vitro: NAMI-A can significantly affect tumor cells with metastatic ability.
The half lifetime of NAMI-A elimination from the lungs is longer than for liver, kidney, and primary tumor. NAMI-A bound to collagen is active on tumor cells as shown in vitro by an invasion test, using a modified Boyden chamber and Matrigel, and it inhibits the matrix metallo-proteinases MMP-2 and MMP-9 at micromolar concentrations. [1] The ruthenium drug NAMI-A inhibits the adhesion and migration of colorectal cancer cells. NAMI-A decreases α5β1 integrin expression and FAK auto-phosphorylation on Tyr 397. [2]
In vivo: The reference for NAMI-A is 35 mg/kg/day. [1]
Pharmaceutical Applications
NAMI-A has shown activity in the treatment of metastatic cancer and has completed phase I clinical trials
in the Netherlands. It has been shown that the complex is relatively nontoxic. Significantly higher doses than
cisplatin (above 500 mg/m
2/day) lead to side effects such as blisters on the extremities. Within the study, the
ruthenium complex was administered intravenously over a period of 3 h in a 0.9% saline solution (pH～4) .
The NAMI-A is synthesised by reacting RuCl33H20 with HCl and DMSO (dimethylsulfoxide). This reaction
results in the trans complex Imidazolium trans-imidazoledimethyl sulfoxide-tetrachlororuthenate(III)
(NAMI-A) .
It is interesting to note that Imidazolium trans-imidazoledimethyl sulfoxide-tetrachlororuthenate(III) is a
paramagnetic compound and the complex is quickly hydrolysed in water. Initially, one chloride ligand is
replaced by an aquo ligand, but the DMSO ligand is quickly replaced as well. As previously mentioned,
it has been suggested that the complex is activated by bio-reduction of the Ru(III) centre to Ru(II) in the
hypoxic environment of cancer cells. There is not much knowledge at present about the biological target for
Imidazolium trans-imidazoledimethyl sulfoxide-tetrachlororuthenate(III). It is known that it interacts with
the imidazoles of proteins and that the interaction with DNA is only weak, questioning DNA as a primary
target for the ruthenium drug.
Biological Activity
NAMI-A is a potent antimetastatic drug in vivo th at is exhibits little cytotoxicity towards many cancer cell lines. Antimetastatic of NAMI-A is attributed to the formation of adducts with membrane and cytosolic proteins. Nevertheless NAMI-A induces potent and selective cytotoxic effects in several leukemia cell lines. NAMI-A exhibits low toxicity for host tissues.', 'NAMI-A is a ruthenium-based anticancer agent.
References
[1] Sava G et al. Dual Action of NAMI-A in inhibition of solid tumor metastasis: selective targeting of metastatic cells and binding to collagen. Clin Cancer Res. 2003 May;9(5):1898-905. PMID:12738748
[2] Pelillo C et al. Inhibition of adhesion, migration and of α5β1 integrin in the HCT-116 colorectal cancer cells treated with the ruthenium drug NAMI-A. J Inorg Biochem. 2016 Jul;160:225-35. DOI:
10.1016/j.jinorgbio.2016.02.025
