Inhibitory interactions of glutathione derivatives, coumarins and quercetins with dominant onion bulb glutathione S-transferases: a structural analysis

The dominant onion bulb glutathione S-transferases (GSTs) (named as GSTc, GSTd and GSTe) were separated by DEAE cellulose column chromatography, and the inhibitory interactions of glutathione (GSH) derivatives (S-methyl GSH, S-propyl GSH, S-butyl GSH, and S-hexyl GSH), four coumarins (coumarin, 7-hydroxy coumarin, esculetin and scopoletin) were tested with theses GSTs. The activities of GSTs were found to be inhibited differently by different compounds. The longer alkyl chained GSH derivatives viz. S-hexyl GSH (IC50 25 μM) followed by S-butyl GSH (IC50 28 μM) showed stronger inhibitory effect on the 1-chloro-2,4-dinitrobenzene (CDNB) conjugated activity of GSTe than shorter ones (S-propyl and S-methyl GSH). Among the coumarins tested, only esculetin had very strong inhibitory effects on GSTc and GSTd with IC50 values of 25 and 28 μM, respectively, but the activity of GSTe was poorly inhibited by this compound. Among the quercetins, quercetin-4′-clucoside showed strongest inhibitory effect on the activities of GSTc and GSTd with IC50s of 8.6 and 7.1 μm, respectively. The IC50s of quercetin, quercetin-3βD-glucoside and quercetin-3,4′-diglucoside were 21.1, 76.3, 76 μm on GSTc, respectively and 20.4, 69.3, 67.7 μm on GSTd, respectively. The structure-activity relationships suggested that hydroxyl groups at C6 and C7 positions of the coumarin skeleton played an important role in the expression of GST inhibitory activity. On the other hand, addition of glucoside at C4′ position of quercetin increased inhibitory activities on GSTc and GSTd. [Rohman MM, Hossain MD, Fujita M. Inhibitory interactions of glutathione derivatives, coumarins and quercetins with dominant onion bulb glutathione S-transferases: a structural analysis. Nature and Science 2010; 8(12):107-114]. (ISSN: 1545-0740).