Effects of derivatives of kahweol and cafestol on the activity of glutathione S-transferase in mice.
The coffee constituents cafestol and kahweol are inducers of the activity of the detoxifying enzyme, glutathione S-transferase in laboratory animals. The two active functional groups, furan and glycol, on opposite ends of the diterpene nucleus of these two compounds have been modified. The resulting derivatives were evaluated for their ability to induce glutathione S-transferase activity in different tissues of the ICR/Ha mice. Derivatives of both cafestol and kahweol, which were the products of the modifications on the glycol function, retained much of the inducing properties of the parent compounds in the liver and mucosa of the small bowel. The effects of these compounds on the tissue acid-soluble sulfhydryl level, in general, were similar to those of the parent compounds. Some derivatives of kahweol, however, appeared to have lost their ability to induce increased levels of sulfhydryls in the liver. Catalytic hydrogenation of the furan moiety gave two products, the dihydro and tetrahydro derivatives. Both compounds and their corresponding acetates lost their effectiveness as inducers of glutathione S-transferase activity. In contrast, these compounds still retained their ability to induce increased levels of acid-soluble sulfhydryls in both the liver and the mucosa of the small bowel. These findings indicate that the furan moiety of cafestol and kahweol is vital to their biological activity as inducers of increased glutathione S-transferase activity.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004224:Diterpenes / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005982:Glutathione Transferase / Q000096:biosynthesis*; D007413:Intestinal Mucosa / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D051379:Mice; D008813:Mice, Inbred ICR; D013270:Stomach / Q000201:enzymology; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000378:metabolism
D004224:Diterpenes; D013438:Sulfhydryl Compounds; C053401:kahweol; C053400:cafestol; D005982:Glutathione Transferase