Journal Article

Automated approach for the evaluation of glutathione-S-transferase P1-1 inhibition by organometallic anticancer compounds

Marchetti, Fabio, Dyson, Paul J., Saraiva, M. Lúcia M. F. S., Pereira, Sarah A. P., Biancalana, Lorenzo, Baptista L, A. Catarina

2022

Overview

A novel automated method based on sequential injection analysis (SIA), a non-segmented flow injection technique, was developed to evaluate glutathione S-transferase P1-1 (GST P1-1) activity in the presence of organometallic complexes with putative anticancer activity. The assay is based on the reaction of L-glutathione (GSH) and 1-chloro-2,4-dinitrobenzene (CDNB) in the presence of GST P1-1 to afford the GS-DNB conjugate and the reaction may be monitored by an increase in absorbance at 340 nm. A series of ruthenium, iron, osmium and iridium complexes were evaluated as GST P1-1 inhibitors by evaluating their half-maximal inhibitory concentration (IC 50 ). An iridium compound displays the lowest IC 50 value of 6.7 ± 0.7 µM and an iron compound displays the highest IC 50 value of 275 ± 9 µM. The SIA method is simple to use, robust, reliable, and efficient and uses fewer reagents than batch methods and each analysis takes only 5 minutes.

• Publisher: Taylor & Francis,Taylor & Francis Ltd,Taylor & Francis Group
• Subject: 1-Chloro-2,4-dinitrobenzene / anticancer metal complexes / Antitumor activity / Automation / Cancer / Dinitrobenzene / enzyme inhibition assays / Enzymes / Glutathione / glutathione S-transferase P1-1 / Glutathione transferase / Iron / Metabolism / Organometallic complexes / Osmium / Pharmaceutical sciences / Reagents / Research Paper / Sequential injection analysis (SIA)