PMID- 19860413
OWN - NLM
STAT- MEDLINE
DCOM- 20100309
LR  - 20211020
IS  - 1520-5010 (Electronic)
IS  - 0893-228X (Print)
IS  - 0893-228X (Linking)
VI  - 22
IP  - 12
DP  - 2009 Dec
TI  - Structural identification of Diindole agonists of the aryl hydrocarbon receptor 
      derived from degradation of indole-3-pyruvic acid.
PG  - 1905-12
LID - 10.1021/tx9000418 [doi]
AB  - Aerobic incubation of the tryptophan transamination/oxidation product 
      indole-3-pyruvic acid (I3P) at pH 7.4 and 37 degrees C yielded products with 
      activity as Ah receptor (AHR) agonists. The extracts were fractionated using HPLC 
      and screened for AHR agonist activity. Two compounds were identified as agonists: 
      1,3-di(1H-indol-3-yl)propan-2-one (1) and 
      1-(1H-indol-3-yl)-3-(3H-indol-3-ylidene) propan-2-one (2), with the potency of 2 
      being 100-fold > 1 [ Nguyen et al. ( 2009 ) Chem. Res. Toxicol. , DOI: 
      10.1021/tx900043s . ]. Both 1 and 2 showed UV spectra indicative of indole. The 
      molecular formulas were established by high-resolution mass spectrometry (HRMS), 
      and the structures were determined by a combination of NMR methods, including 
      (1)H, natural abundance (13)C, and two-dimensional methods. An intermediate in 
      the oxidation of I3P to 1 is 3-hydroxy-2,4-di(1H-indol-3-yl)butanal (HRMS 
      established the presence of a compound with the formula C(20)H(19)N(2)O(2)). 
      Compound 1 was converted to 2 in air or (faster) with mild oxidants, and 2 could 
      be further oxidized to 1,3-di(3H-indol-3-ylidene)propan-2-one. Determination of 
      the structures allowed estimation of the molar Ah receptor agonist activity of 
      these natural products, similar in potency to known classical AHR inducers.
FAU - Chowdhury, Goutam
AU  - Chowdhury G
AD  - Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt 
      University School of Medicine, Nashville, Tennessee 37232-0146, USA.
FAU - Dostalek, Miroslav
AU  - Dostalek M
FAU - Hsu, Erin L
AU  - Hsu EL
FAU - Nguyen, Linh P
AU  - Nguyen LP
FAU - Stec, Donald F
AU  - Stec DF
FAU - Bradfield, Christopher A
AU  - Bradfield CA
FAU - Guengerich, F Peter
AU  - Guengerich FP
LA  - eng
GR  - P30 ES000267/ES/NIEHS NIH HHS/United States
GR  - P30 CA014520/CA/NCI NIH HHS/United States
GR  - R37 CA090426-09/CA/NCI NIH HHS/United States
GR  - R37 ES005703/ES/NIEHS NIH HHS/United States
GR  - T32ES007015/ES/NIEHS NIH HHS/United States
GR  - R37 CA090426/CA/NCI NIH HHS/United States
GR  - S10 RR019022/RR/NCRR NIH HHS/United States
GR  - T32 CA009135/CA/NCI NIH HHS/United States
GR  - S10RR019022/RR/NCRR NIH HHS/United States
GR  - T32 ES007015/ES/NIEHS NIH HHS/United States
GR  - P30 ES000267-42/ES/NIEHS NIH HHS/United States
GR  - R37ES005703/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Chem Res Toxicol
JT  - Chemical research in toxicology
JID - 8807448
RN  - 0 (1,3-di(1H-indol-3-yl)propan-2-one)
RN  - 0 (1-(1H-indol-3-yl)-3-(3H-indol-3-ylidene)propan-2-one)
RN  - 0 (Indoles)
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 4QM0LT13A8 (indol-3-yl pyruvic acid)
SB  - IM
MH  - Hydrogen-Ion Concentration
MH  - Indoles/*chemistry/isolation & purification/metabolism
MH  - Magnetic Resonance Spectroscopy
MH  - Mass Spectrometry
MH  - Receptors, Aryl Hydrocarbon/*agonists/metabolism
MH  - Spectrophotometry, Ultraviolet
MH  - Temperature
PMC - PMC2801742
MID - NIHMS155733
EDAT- 2009/10/29 06:00
MHDA- 2010/03/10 06:00
PMCR- 2010/12/21
CRDT- 2009/10/29 06:00
PHST- 2009/10/29 06:00 [entrez]
PHST- 2009/10/29 06:00 [pubmed]
PHST- 2010/03/10 06:00 [medline]
PHST- 2010/12/21 00:00 [pmc-release]
AID - 10.1021/tx9000418 [doi]
PST - ppublish
SO  - Chem Res Toxicol. 2009 Dec;22(12):1905-12. doi: 10.1021/tx9000418.