The inhibitory capacity of organometallic compounds with anticancer features in GST P1-1 enzyme activity: An automatic approach

Glutathione S-transferases (GSTs) are an important group of isoenzymes that play an essential role in the detoxification of carcinogens. In this way, GST P1-1 is considered a suitable and excellent targetable biomarker to differentiate cancer from normal cells. Ruthenium-, iron-, osmium- and iridium-based compounds are considered promising candidates for the next generation of metal anticancer drugs in order to overcome the side effects produced by the anticancer platinum drugs used in clinic. In this work, it was developed a miniaturized approach based on sequential injection analysis (SIA) for the determination of the half maximal inhibitory concentration (IC50) of GSTs. Beyond the advantages presented by SIA systems such as versatility, simplicity, robustness, reliability and efficiency, this specific one present two more important advantages allowing the use of three times less reagent solutions than in batch method and reducing the analysis time from 8 minutes to 5 minutes. The newly developed method was applied to 22 ruthenium, iron, osmium and iridium derivates compounds ethacrynic acid (EA) and flurbiprofen, a cyclooxygenase inhibitor, were shown to be potent GST P1-1 inhibitors. The iridium compound tested is the strongest inhibitor of GST P1-1 (IC50 = 6.7 ± 0.7 µM) in the present work, more effective than EA itself and the ruthenium analogue.