- Inhibition of glutathione S-transferase in rat hepatocytes by a glycine-tetrazole modified S-alkyl-GSH analogue.
Inhibition of glutathione S-transferase in rat hepatocytes by a glycine-tetrazole modified S-alkyl-GSH analogue.
Bioorganic & medicinal chemistry letters (2002-06-01)
Danny Burg, Liesbeth Hameetman, Dmitri V Filippov, Gijs A van der Marel, Gerard J Mulder
PMID12039566
ABSTRACT
Glutathione (GSH) conjugates inhibit enzymes that are involved in drug metabolism and drug resistance, but their cellular uptake is very low. To improve membrane-permeability, we synthesized a novel GSH-conjugate analogue with a tetrazole carboxylate isostere at the glycine position. Introduction of the tetrazole decreases inhibitory potency towards CDNB conjugation by glutathione S-transferase. However, the tetrazole derivative inhibited 2-bromoisovalerylurea conjugation in rat liver cytosol, as well as in hepatocytes.
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