T3DB: Secalonic Acid D

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (4)XML

Targets (4)

Record Information

Version

2.0

Creation Date

2010-05-26 16:48:09 UTC

Update Date

2014-12-24 20:26:31 UTC

Accession Number

T3D3774

Identification

Common Name

Secalonic Acid D

Class

Small Molecule

Description

Secalonic acid D (SAD) is a mycotoxin produced by the fungus Pencillium oxalicum, which is a common contaminant in corn and other grains. Secalonic acid D is a human teratogen that induces cleft palate. (1)

Compound Type

Ester
Ether
Fungal Toxin
Mycotoxin
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(7,7'-Bi-4aH-xanthene)-4a,4'a-dicarboxylic acid, 2,2',3,3',4,4',9,9'-octahydro-1,1',4,4',8,8'-hexahydroxy-3,3'-dimethyl-9,9'-dioxo-, dimethyl ester, (3S-(3-alpha,4-beta,4a-beta,7(3'R,4'S,4'aS)))
Ergochrome AA (2,2')-5-beta,6-alpha,10-beta-5',6'-alpha,10'-beta
SAD
Secalonate D
Secalonic acid D
Secalonic acid D mycotoxin
Secalonsaure D

Chemical Formula

C₃₂H₃₀O₁₄

Average Molecular Mass

638.572 g/mol

Monoisotopic Mass

638.164 g/mol

CAS Registry Number

35287-69-5

IUPAC Name

methyl 4,8,9-trihydroxy-3-methyl-1-oxo-7-[4,8,9-trihydroxy-4a-(methoxycarbonyl)-3-methyl-1-oxo-2,3,4,4a-tetrahydro-1H-xanthen-7-yl]-2,3,4,4a-tetrahydro-1H-xanthene-4a-carboxylate

Traditional Name

secalonic acid D

SMILES

COC(=O)C12OC3=C(C(O)=C(C=C3)C3=C(O)C4=C(OC5(C(O)C(C)CC(=O)C5=C4O)C(=O)OC)C=C3)C(O)=C1C(=O)CC(C)C2O

InChI Identifier

InChI=1S/C32H30O14/c1-11-9-15(33)21-25(37)19-17(45-31(21,27(11)39)29(41)43-3)7-5-13(23(19)35)14-6-8-18-20(24(14)36)26(38)22-16(34)10-12(2)28(40)32(22,46-18)30(42)44-4/h5-8,11-12,27-28,35-40H,9-10H2,1-4H3

InChI Key

InChIKey=NFZJAYYORNVZNI-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as xanthenes. These are polycyclic aromatic compounds containing a xanthene moiety, which consists of two benzene rings joined to each other by a pyran ring.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Benzopyrans

Sub Class

1-benzopyrans

Direct Parent

Xanthenes

Alternative Parents

Substituents

Xanthene
1-hydroxy-4-unsubstituted benzenoid
Alkyl aryl ether
Beta-hydroxy acid
Dicarboxylic acid or derivatives
Benzenoid
Hydroxy acid
Cyclic alcohol
Vinylogous acid
Methyl ester
Carboxylic acid ester
Secondary alcohol
Ketone
Ether
Enol
Oxacycle
Carboxylic acid derivative
Polyol
Organic oxygen compound
Hydrocarbon derivative
Alcohol
Carbonyl group
Organic oxide
Organooxygen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.28 g/L	ALOGPS
logP	1.62	ALOGPS
logP	1.19	ChemAxon
logS	-3.4	ALOGPS
pKa (Strongest Acidic)	5.57	ChemAxon
pKa (Strongest Basic)	-3.5	ChemAxon
Physiological Charge	-2	ChemAxon
Hydrogen Acceptor Count	12	ChemAxon
Hydrogen Donor Count	6	ChemAxon
Polar Surface Area	226.58 Å²	ChemAxon
Rotatable Bond Count	5	ChemAxon
Refractivity	156.5 m³·mol⁻¹	ChemAxon
Polarizability	63.29 Å³	ChemAxon
Number of Rings	6	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-0000209000-fbd21faaff04fd0994e8	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-009i-1341429000-8e5a7a842c2b59ca5334	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-00di-1090000000-db059c3481746c5817f0	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-000i-0000119000-2f2c44ebedcf7b00751c	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00p0-0254419000-2a03bc319b29191e5c61	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-014i-1559250000-6cfd148c809a2998b5dd	2016-08-03	View Spectrum

Toxicity Profile

Route of Exposure

Oral, dermal, inhalation, and parenteral (contaminated drugs). (4)

Mechanism of Toxicity

Secalonic acid D (SAD) is though to induce cleft palate by causing the formation of smaller palatal shelves that fail to elevate and fuse. This inhibited palatal shelf growth is a result of the of SAD causing reduced proliferation of embryonic palatal mesenchymal (HEPM) cells. SAD binds to and phosphorylates cAMP response element binding protein (CREB), an important transcription factor required for the expression of numerous genes including proliferating cell nuclear antigen (PCNA) gene. The phosphorylation of CREB by SAD prevents it from forming the necessary transcription factor-cAMP response element complex at transcription start sites, so these genes are not expressed. This leads to reduced palatal mesenchymal cell number causing reduced palatal shelf growth and thus cleft palate. (1, 2, 3)

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Secalonic acid D (SAD) is a mycotoxin produced by the fungus Pencillium oxalicum, which is a common contaminant in corn and other grains. (1)

Minimum Risk Level

Not Available

Health Effects

Secalonic acid D is a human teratogen that induces cleft palate. (1)

Symptoms

Cleft palate is a congenital deformity characterized by a gap on the roof of the mouth that is present at birth. (3)

Treatment

Cleft palate can be treated with corrective surgery. (3)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

73431

ChEMBL ID

Not Available

ChemSpider ID

Not Available

KEGG ID

Not Available

UniProt ID

Not Available

OMIM ID

ChEBI ID

Not Available

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

T3D3774.pdf

General References

Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. [15880679 ]
Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. [12388835 ]
Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. [11861983 ]
Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Cyclic AMP-responsive element-binding protein 1

General Function:: Transcriptional activator activity, rna polymerase ii transcription factor binding
Specific Function:: Phosphorylation-dependent transcription factor that stimulates transcription upon binding to the DNA cAMP response element (CRE), a sequence present in many viral and cellular promoters. Transcription activation is enhanced by the TORC coactivators which act independently of Ser-133 phosphorylation. Involved in different cellular processes including the synchronization of circadian rhythmicity and the differentiation of adipose cells.
Gene Name:: CREB1
Uniprot ID:: P16220
Molecular Weight:: 36687.86 Da

References

Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. [15880679 ]
Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. [12388835 ]
Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. [11861983 ]

Target Details

2. Cyclic AMP-responsive element-binding protein 3

General Function:: Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:: Endoplasmic reticulum (ER)-bound transcription factor that plays a role in the unfolded protein response (UPR). Involved in cell proliferation and migration, tumor suppression and inflammatory gene expression. Plays also a role in the human immunodeficiency virus type 1 (HIV-1) virus protein expression and in the herpes simplex virus-1 (HSV-1) latent infection and reactivation from latency. Isoform 2 plays a role in the unfolded protein response (UPR). Isoform 2 acts as a positive regulator of LKN-1/CCL15-induced chemotaxis signaling of leukocyte cell migration. Isoform 2 may play a role as a cellular tumor suppressor that is targeted by the hepatitis C virus (HSV) core protein. Isoform 2 represses the VP16-mediated transactivation of immediate early genes of the HSV-1 virus by sequestring host cell factor-1 HCFC1 in the ER membrane of sensory neurons, thereby preventing the initiation of the replicative cascade leading to latent infection. Isoform 3 functions as a negative transcriptional regulator in ligand-induced transcriptional activation of the glucocorticoid receptor NR3C1 by recruiting and activating histone deacetylases (HDAC1, HDAC2 and HDAC6). Isoform 3 decreases the acetylation level of histone H4. Isoform 3 does not promote the chemotactic activity of leukocyte cells.Processed cyclic AMP-responsive element-binding protein 3: acts as a transcription factor that activates unfolded protein response (UPR) target genes during endoplasmic reticulum (ER) stress response. Promotes cell survival against ER stress-induced apoptotic cell death during UPR. Activates transcription from CRE and C/EBP-containing reporter genes. Induces transcriptional activation of chemokine receptors. Activates transcription of genes required for reactivation of the latent HSV-1 virus. Down-regulates Tat-dependent transcription of the HIV-1 LTR by interacting with HIV-1 Tat. It's transcriptional activity is inhibited by CREBZF in a HCFC1-dependent manner, by the viral transactivator protein VP16 and by the HCV core protein. Binds DNA to the cAMP response element (CRE) (consensus: 5'-GTGACGT[AG][AG]-3') and C/EBP sequences present in many viral and cellular promoters. Binds to the unfolded protein respons element (UPRE) consensus sequences sites. Binds DNA to the 5'-CCAC[GA]-3'half of ERSE II (5'-ATTGG-N-CCACG-3'). Associates with chromatin to the HERPUD1 promoter.
Gene Name:: CREB3
Uniprot ID:: O43889
Molecular Weight:: 43916.65 Da

References

Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. [15880679 ]
Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. [12388835 ]
Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. [11861983 ]

Target Details

3. Cyclic AMP-responsive element-binding protein 5

General Function:: Transcription factor activity, sequence-specific dna binding
Specific Function:: Binds to the cAMP response element and activates transcription.
Gene Name:: CREB5
Uniprot ID:: Q02930
Molecular Weight:: 56918.115 Da

References

Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. [15880679 ]
Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. [12388835 ]
Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. [11861983 ]

4. activator protein 1 (Protein Group)

General Function:: Transcriptional activator activity, rna polymerase ii transcription regulatory region sequence-specific binding
Specific Function:: This protein binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Binds to the Tax-responsive element (TRE) of HTLV-I. Mediates PKA-induced stimulation of CRE-reporter genes. Represses the expression of FTH1 and other antioxidant detoxification genes. Triggers cell proliferation and transformation.
Included Proteins:: P18846 , P15336 , P18847 , P18848 , Q9Y2D1 , P18850 , P17544 , Q8WYK2 , P01100 , P05412

References

Dhulipala VC, Maddali KK, Welshons WV, Reddy CS: Secalonic acid D blocks embryonic palatal mesenchymal cell-cycle by altering the activity of CDK2 and the expression of p21 and cyclin E. Birth Defects Res B Dev Reprod Toxicol. 2005 Jun;74(3):233-42. [15880679 ]
Hanumegowda UM, Dhulipala VC, Reddy CS: Mechanism of secalonic acid D-induced inhibition of transcription factor binding to cyclic AMP response element in the developing murine palate. Toxicol Sci. 2002 Nov;70(1):55-62. [12388835 ]
Hanumegowda UM, Judy BM, Welshons WV, Reddy CS: Selective inhibition of murine palatal mesenchymal cell proliferation in vitro by secalonic acid D. Toxicol Sci. 2002 Mar;66(1):159-65. [11861983 ]

Secalonic Acid D (T3D3774)

Structure for T3D3774: Secalonic Acid D

Targets

References

References

References

References