2-Acetylaminofluorene

2-Acetylaminofluorene
Names
Systematic IUPAC name
N-(9H-fluoren-2-yl)acetamide[1]
Other names
2-Acetaminofluorene[2]

N-2-Fluorenylacetamide[2]

N-Acetyl-2-aminofluorene[3]
Identifiers
53-96-3 YesY
Abbreviations 2-AAF
2807677
ChEBI CHEBI:17356 YesY
ChEMBL ChEMBL311469 YesY
ChemSpider 5686 YesY
EC Number 200-188-6
Jmol interactive 3D Image
Image
KEGG C02778 YesY
MeSH 2-Acetylaminofluorene
PubChem 5897
RTECS number AB9450000
UN number 3077
Properties
C15H13NO
Molar mass 223.28 g·mol−1
Appearance Vivid, light brown, opaque crystals
Melting point 192 to 196 °C (378 to 385 °F; 465 to 469 K)
log P 3.264
Hazards
Main hazards potential occupational carcinogen[3]
GHS pictograms
GHS signal word Danger
H302, H350
P201, P308+313
T N
R-phrases R45, R22, R51/53
S-phrases S53, S36/37/39, S45
US health exposure limits (NIOSH):
[OSHA-Regulated Carcinogen][3]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

2-Acetylaminofluorene (AAF,[4] 2-AAF) is a carcinogenic and mutagenic derivative of fluorene. It is used as a biochemical tool in the study of carcinogenesis. It induces tumors in a number of species in the liver, bladder and kidney. The metabolism of this compound in the body by means of biotransformation reactions is the key to its carcinogenicity. 2-AAF is a substrate for cytochrome P-450 (CYP) enzyme, which is a part of a super family found in almost all organisms. This reaction results in the formation of N-hydroxy-2-acetylaminofluorene which is a proximal carcinogen and is more potent than the parent molecule. The N-hydroxy metabolite undergoes several enzymatic and non-enzymatic rearrangements. It can be O-acetylated by cytosolic N-acetyltransferase enzyme to yield N-acetyl-N-acetoxyaminofluorene. This intermediate can spontaneously rearrange to form the arylamidonium ion and a carbonium ion which can interact directly with DNA to produce DNA adducts. In addition to esterification by acetylation, the N-hydroxy derivative can be O-sulfated by cytosolic sulfur transferase enzyme giving rise to the N-acetyl-N-sulfoxy product.

In addition, the cytosolic N,O-aryl hydroxamic acid acyltransferase enzyme catalyzes the transfer of the acetyl group from the N atom of the N-OH-2-AAF to the O atom of the N-OH group to produce N-acetoxy-2-aminofluorene (N-OH-2-AF). This reactive metabolite spontaneously decomposes to form a nitrenium ion which will also react with DNA. However, the product of this latter reaction is the deacetylated aminofluorene adduct. The interconversion of amide and amine metabolites of 2-AAF can further occur via the microsomal enzyme deacetylase producing the N-hydroxy metabolite of the amine derivative. Subsequent esterification of the aryl hydroxylamine by sulfur transferase yields the sulfate ester which also spontaneously decompose to form nitrenium ion. The reactive nitrenium, carbonium and arylamidonium ion metabolites of 2-AAF react with the nucleophilic groups in DNA, proteins and endogenous thiols like glutathione. Other metabolites such as the N,O-glucuronide, although not directly activated products, can be important in the carcinogenic process because they are capable of degradation to proximal N-hydroxy metabolites. This metabolite is presumed to be involved in formation of bladder tumors. The mechanism for this is thought to involve degradation of glucuronide in the bladder due to acidic pH of urine.

See also

References

  1. ↑ "2-Acetylaminofluorene - PubChem Public Chemical Database". The PubChem Project. USA: National Center for Biotechnology Information. Descriptors Computed from Structure.
  2. 1 2 "NIOSH Pocket Guide to Chemical Hazards". Centers for Disease Control and Prevnetion.
  3. 1 2 3 "NIOSH Pocket Guide to Chemical Hazards #0007". National Institute for Occupational Safety and Health (NIOSH).
  4. ↑ Logan, Carolynn M.; Rice, M. Katherine (1987). Logan's Medical and Scientific Abbreviations. Philadelphia: J. B. Lippincott Company. p. 3. ISBN 0-397-54589-4.
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