Bioorganic & Medicinal Chemistry Letters 2002-06-17

Inhibition of glutathione S-transferase in rat hepatocytes by a glycine-tetrazole modified S-alkyl-GSH analogue.

Danny Burg, Liesbeth Hameetman, Dmitri V Filippov, Gijs A van der Marel, Gerard J Mulder

Index: Bioorg. Med. Chem. Lett. 12(12) , 1579-82, (2002)

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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.