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

J Enzyme Inhib Med Chem. 2022 Dec;37(1):1527-1536. doi: 10.1080/14756366.2022.2073443.

Abstract

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 (IC50). An iridium compound displays the lowest IC50 value of 6.7 ± 0.7 µM and an iron compound displays the highest IC50 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.

Keywords: Sequential injection analysis (SIA); anticancer metal complexes; enzyme inhibition assays; glutathione S-transferase P1-1.

MeSH terms

  • Glutathione
  • Glutathione S-Transferase pi
  • Glutathione Transferase*
  • Iridium
  • Organometallic Compounds* / pharmacology

Substances

  • Organometallic Compounds
  • Iridium
  • Glutathione S-Transferase pi
  • Glutathione Transferase
  • Glutathione

Grants and funding

This work received financial support from the project with reference PTDC/QUIQAN/ 30163/2017 - Tailored NanoGumbos: The green key to wound infections chemosensing, supported by national funds by FCT/MCTES and co-supported by Fundo Europeu de Desenvolvimento Regional (FEDER) through the Operational Competitiveness Program (COMPETE)–reference number P OCI-01-0145-FEDER-030163.