Secalonic Acid D
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Basic Info
| Common Name | Secalonic Acid D(F05014) |
| 2D Structure | |
| 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. (A3088) |
| FRCD ID | F05014 |
| CAS Number | 35287-69-5 |
| PubChem CID | 73431 |
| Formula | C32H30O14 |
| IUPAC Name | methyl (3S,4R,4aR)-7-[(5R,6S,10aR)-1,5,9-trihydroxy-10a-methoxycarbonyl-6-methyl-8-oxo-6,7-dihydro-5H-xanthen-2-yl]-4,8,9-trihydroxy-3-methyl-1-oxo-3,4-dihydro-2H-xanthene-4a-carboxylate |
| InChI Key | NFZJAYYORNVZNI-OCHURCMPSA-N |
| InChI | 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/t11-,12-,27+,28+,31+,32+/m0/s1 |
| Canonical SMILES | CC1CC(=O)C2=C(C3=C(C=CC(=C3O)C4=C(C5=C(C=C4)OC6(C(C(CC(=O)C6=C5O)C)O)C(=O)OC)O)OC2(C1O)C(=O)OC)O |
| Isomeric SMILES | C[C@H]1CC(=O)C2=C(C3=C(C=CC(=C3O)C4=C(C5=C(C=C4)O[C@]6([C@@H]([C@H](CC(=O)C6=C5O)C)O)C(=O)OC)O)O[C@]2([C@@H]1O)C(=O)OC)O |
| Synonyms |
Ergochrome AA (2,2')-5-beta,6-alpha,10-beta-5',6'-alpha,10'-beta
(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)))
Secalonic acid D
SECALONSAURE D
UNII-HZP8L3M5ME
Secalonic acid D mycotoxin
CCRIS 4937
HZP8L3M5ME
35287-69-5
NSC 159631
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Benzopyrans |
| Subclass | 1-benzopyrans |
| Intermediate Tree Nodes | Dibenzopyrans |
| Direct Parent | Xanthenes |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| 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 |
| Description | This compound 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 638.578 |
| Hydrogen Bond Donor Count | 6 |
| Hydrogen Bond Acceptor Count | 14 |
| Rotatable Bond Count | 5 |
| Complexity | 1300 |
| Monoisotopic Mass | 638.164 |
| Exact Mass | 638.164 |
| XLogP | 3.1 |
| Formal Charge | 0 |
| Heavy Atom Count | 46 |
| Defined Atom Stereocenter Count | 6 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB- | 0.7807 |
| Human Intestinal Absorption | HIA+ | 0.8900 |
| Caco-2 Permeability | Caco2+ | 0.5093 |
| P-glycoprotein Substrate | Substrate | 0.7987 |
| P-glycoprotein Inhibitor | Inhibitor | 0.6333 |
| Inhibitor | 0.5325 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9279 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.6218 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8361 |
| CYP450 2D6 Substrate | Non-substrate | 0.8730 |
| CYP450 3A4 Substrate | Substrate | 0.6508 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8504 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.6355 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8578 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7023 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.7445 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.6305 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9886 |
| Non-inhibitor | 0.8858 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.9486 |
| Fish Toxicity | High FHMT | 0.9528 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9848 |
| Honey Bee Toxicity | High HBT | 0.7933 |
| Biodegradation | Not ready biodegradable | 0.9780 |
| Acute Oral Toxicity | I | 0.7914 |
| Carcinogenicity (Three-class) | Danger | 0.5123 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.9508 | LogS |
| Caco-2 Permeability | 0.6006 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 4.4318 | LD50, mol/kg |
| Fish Toxicity | 0.2989 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 1.1964 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Oxidative degradation and detoxification of mycotoxins using a novel source of ozone. | Food Chem Toxicol | 1997 Aug | 9350226 |
| Separation of mycotoxin-containing sources in grain dust and determination of their mycotoxin potential. | Environ Health Perspect | 1986 Apr | 3709472 |
| [Production of secalonic acid D by strains of Penicillium oxalicum and its toxic effects on chick embryos]. | Vet Med (Praha) | 1985 Sep | 3931337 |
| Mycotoxins in grain dust: method for analysis of aflatoxins, ochratoxin A, zearalenone, vomitoxin, and secalonic acid D. | J Assoc Off Anal Chem | 1984 Sep-Oct | 6238942 |
| Secalonic acid D: natural contaminant of corn dust. | Appl Environ Microbiol | 1982 Oct | 7149710 |
Targets
- 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
- Mechanism of Action:
- 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.
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 ]
- Uniprot ID:
- P18846; P15336; P18847; P18848; Q9Y2D1; P18850; P17544; Q8WYK2; P01100; P05412
- Mechanism of Action:
- 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.
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 ]
- 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
- Mechanism of Action:
- 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.
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 ]
- 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
- Mechanism of Action:
- 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.
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 ]