New 9-stubstituted 3-N,O-diacetylhydroxylaminofluorenes: enhanced electrophilicity and mutagenicity. Derivatives of fluorene. 38.
The compound 2-acetamidofluorene is a potent hepatocarcinogen; its N-acetoxy derivative (2-NOAc-AAF), a model ultimate form of the carcinogen, is strongly mutagenic and is chemically reactive with nucleophiles. The isomeric 3-acetamidofluorene is a mammary carcinogen, but is not hepatocarinogenic; its N-acetoxy derivative (3-NOAc-AAF) is not reactive with nucleophiles. Derivatives of 3-NOAc-AAF containing electron-donating groups in positions conjugated with the 3-position have been synthesized. These show increased electrophilicity and mutagenicity. Thus, by electronic manipulation of the leaving-group capacity of the -OAc group of 3-NOAc-AAF, we have obtained compounds with increased biological activity, as well as increased chemical reactivity. Future experiments could show whether in vivo effects of these derivatives of 3-NOAc-AAF are more like the effects of 2-NOAc-AAF or of 3-NOAc-AAF.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006881:Hydroxyacetylaminofluorene / Q000031:analogs & derivatives*; D009153:Mutagens; D051381:Rats; D013329:Structure-Activity Relationship
D009153:Mutagens; D006881:Hydroxyacetylaminofluorene; D015073:2-Acetylaminofluorene