Structure‐activity relationships of (1′S)‐acetoxychavicol acetate for the decrease in intracellular glutathione level in Ehrlich ascites tumor cells

Abstract

We examined the structure‐activity relationships of (1′S)‐Acetoxychavicol acetate ((S)‐ACA), an anticarcinogenic compound naturally obtained from the rhizomes and the seeds of the Zingiberaceae plant, for the decrease in intracellular GSH making comparison with the activity of some synthetic‐related compounds in Ehrlich ascites tumor cells. (R)‐ACA and rac‐ACA caused the inhibition of cell viability similarly as (S)‐ACA. In previous study, we have shown that (S)‐ACA caused a rapid decrease in GSH level in less than 15 min after (S)‐ACA exposure. The addition of (R)‐ACA and rac‐ACA also caused the decrease in cellular GSH in Ehrlich ascites tumor cells. (S)‐ACA and (R)‐ACA induced cell death was reversed by the addition of N‐acetlycysteine. Therefore, we examined the inhibitory activities of rac‐ACA and its 9 derivatives toward the viability, the intracellular GSH level and GR activity in the cells was remarkably decreased with the treatment of rac‐ACA, rac‐3,4‐ACA, rac‐2,4‐ACA, rac‐trp‐7c‐ACA and rac‐BCB, but not changed with 20 μM concentration of 3′‐ACA, rac‐m‐ACA, rac‐o‐ACA, rac‐ADC, and rac‐DHACA. We also found that there is a highly significant correlation between GR activities and GSH levels and suggested that the decrease in the intracellular GSH levels was mainly caused by the decrease in the activity of GR in less than 15 min after ACAs exposure in Ehrlich ascites tumor cells.