Isolation and biological evaluation of potential cancer chemopreventive agents from ambrette musk residue.
Two nitroaromatic compounds, 1-(1,1-dimethylethyl)-3,5-dimethyl-2,4-dinitrobenzene (1) and 1-[4-(1,1-dimethylethyl)-2,6-dimethyl-3,5-dinitrophenyl]ethanone or musk ketone (2), were isolated from ambrette musk residue, which is widely used in the food and cosmetics industry. The ability of 1 and 2 to induce increased activity of the detoxifying enzyme glutathione S-transferase was tested in A/J mice. Enzyme induction in the cytosols of liver, forestomach, lung, colon, and small intestinal mucosa was determined. Biological evaluation revealed that both compounds exhibit high activity as glutathione S-transferase inducers in liver and small intestinal mucosa. The effects of 1 and 2 on the levels of acid-soluble sulfhydryl in the five mouse tissues were also determined. Both compounds slightly elevated sulfhydryl levels in the small intestinal mucosa but significantly decreased the sulfhydryl levels in the other tissues. Because the ability of anticarcinogenic compounds to induce an increase in the detoxifying enzyme activity correlates with their tumor inhibitory activity, 1 and 2 may be potential cancer chemopreventive agents.
Zheng
G Q
GQ
LKT Laboratories Inc., Minneapolis, MN 55413.
Kenney
P M
PM
Lam
L K
LK
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D004136:Dinitrobenzenes / Q000032:analysis* / Q000302:isolation & purification* / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000032:analysis; D005982:Glutathione Transferase / Q000096:biosynthesis; D051379:Mice; D014992:Xylenes / Q000302:isolation & purification* / Q000494:pharmacology
D000970:Antineoplastic Agents; D004136:Dinitrobenzenes; D014992:Xylenes; C031448:musk ketone; C077870:1-(1,1-dimethylethyl)-3,5-dimethyl-2,4-dinitrobenzene; C020422:musk ambrette (artificial); D005982:Glutathione Transferase; D005978:Glutathione