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 ± 0.6 μM to 207 ± 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 ± 1.6 to 207 ± 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.