Automatic evaluation of cyclooxygenase 2 inhibition induced by metal-based anticancer compounds.

An automatic methodology based on micro sequential injection analysis coupled to a lab-on-valve system (termed µSIA-LOV) was developed and used to determine the ability of metal-based anticancer compounds to inhibit cyclooxygenase 2 (COX-2) activity. COX-2 may be involved in pathogenesis of cancer and it is overexpressed in several types of solid tumors. Since platinum-based compounds are extensively used in the treatment of cancer, and ruthenium compounds are considered as promising candidates for next generation of non-targeted anticancer drugs, it is interesting to establish whether COX-2 inhibition is relevant to their mode of action. The µSIA-LOV system was optimized and the IC50 values of each compound were calculated. All the results present RSD values less than 2.5%. IC50 values of 9.7 ±â€¯0.6 µM to 207 ±â€¯3 µM were obtained, with the most active inhibitor for COX-2 being rofecoxib with the metal compounds exhibiting IC50 values in the range 13.7 ±â€¯1.6 to 207 ±â€¯3. The results obtained in this work provide significant information about the mechanism of the studied compounds, mostly ruthenium-based compounds, and the role of COX-2 in their mode of action. Moreover, this work confirmed the potential of the µSIA-LOV system as a simple, versatile, robust, and rapid analytical tool for automating the determination of IC50 values of metal-based compounds.

Towards Light-Activated Ruthenium-Arene (RAPTA-Type) Prodrug Candidates.

Cancer is currently one of the deadliest diseases worldwide. Based on the high incidence of this disease, the side effects associated with current chemotherapies and the appearance of drug resistance, considerable efforts have been directed towards the development of new anticancer drugs with new modes of action. Metal-based compounds are particularly attractive candidates due to their metabolic mechanisms, which differ substantially from those of organic drugs. Of special interest in this context are organometallic ruthenium(II) complexes of the type [Ru(η6 -arene)(pta)Cl2 ] (arene: p-cymene, toluene, benzene, etc.; pta: 1,3,5-triaza-7-phosphaadamantane), which are abbreviated to RAPTA. Complementary to chemotherapy, photoactivated chemotherapy is a technique that has received increasing attention towards the development of treatment for numerous kinds of cancer. With this in mind, a photoactive RAPTA-type complex bearing azide ligands has been designed. The diazide complex, [Ru(η6 -p-cymene)pta-(N3 )2 ], is inert in water, but slowly releases the azide ligand upon exposure to light. Consequently, the in vitro cytotoxicity of the complex in the dark and upon light exposure at λ=450 nm in human cervical carcinoma (HeLa) and noncancerous retinal pigment epithelium (RPE-1) cells was investigated. Although the cytotoxicity of the complex was found to be modest in the dark, an increase in toxicity upon light exposure was observed.