Inhibition of human glutathione transferase P1-1 by novel benzazole derivatives

The human glutathione transferase P1-1 specific inhibitor TER 117 designed for overcoming cytostatic-drug resistance is also a strong inhibitor of glyoxalase I.

gamma-L-Glutamyl-S-(benzyl)-L-cysteinyl-R-(-)-phenylglycine (TER 117) has previously been developed for selective inhibition of human glutathione S-transferase P1-1 (GST P1-1) based on the postulated contribution of this isoenzyme to the development of drug resistance in cancer cells. In the present investigation, the inhibitory effect of TER 117 on the human glyoxalase system was studied. Alth...

Reversible conjugation of ethacrynic acid with glutathione and human glutathione S-transferase P1-1.

The reversibility of the conjugation reaction of the diuretic drug ethacrynic acid (EA), an alpha,beta-unsaturated ketone, with glutathione and glutathione S-transferase P1-1 (GST P1-1) has been studied. When the glutathione conjugate of EA was incubated with a 5-fold molar excess of N-acetyl-L-cysteine or GST P1-1, a time-dependent transfer of EA to N-acetyl-L-cysteine or GST P1-1 was observed...

Nitric Oxide (NO) Releasing Poly ADP-ribose Polymerase 1 (PARP-1) Inhibitors Targeted to Glutathione S-Transferase P1-Overexpressing Cancer Cells

We report the antitumor effects of nitric oxide (NO) releasing derivatives of the PARP-1 inhibitor olaparib (1). Compound 5b was prepared by coupling the carboxyl group of 3b and the free amino group of arylated diazeniumdiolated piperazine 4. Analogue 5a has the same structure except that the F is replaced by H. Compound 13 is the same as 5b except that a Me2N-N(O)═NO- group was added para and...

Induction of Phase II Enzymes Glutathione-S-Transferase and NADPH: Quinone Oxydoreductase 1 with Novel Sulforaphane Derivatives in Human Keratinocytes: Evaluation of the Intracellular GSH Level

Phase II enzymes including NADPH: Quinone Oxydoreductase 1 (NQO1) and Glutathione-S-Transferase (GST) represents a major and natural cellular protection system against deleterious environmental factors which cause skin damages. Sulforaphane is one of the most popular isothiocyanates found in cruciferous vegetables and known for its cytoprotective effects by inducing Phase II enzymes. Five novel...

Mass spectrometric characterization of protein adducts of multiple cytochrome P450-dependent reactive intermediates of diclofenac to human glutathione-S- transferase P1-1 Adapted from: Mass spectrometric characterization of protein adducts of multiple cytochrome P450-dependent reactive intermediates of diclofenac to human glutathione-S-transferase P1-1