Beta-Naphthoflavone

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Beta-Naphthoflavone
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Executive Summary Information

Compound Β-Naphthoflavone
Toxicities Modulation of lipid metabolism with increased cholesterol metabolism and steatosis.
Mechanisms Β-Naphthoflavone is a mechanism of action standard for activation of the AHR transcription factor.
Comments The classic toxicities of thymic atrophy, wasting syndrome, and tumor promotion associated with activation of AHR by dioxins are highly species specific and in part a reflection of the extremely long in vivo half-life of the dioxins.
Feedback Contact Gold Compound Working Group (GCWG)


Beta-Naphthoflavone
Beta-napthoflavone.png


Identifiers
Leadscope Id LS-2162
CAS 6051-87-2
DrugBank DB06732
ChemSpider 2271
Pathway DBs
Assay DBs
PubChem CID 2361
ChEMBL 26260
Omics DBs
Properties
ToxCast Accepted no
Toxic Effect Steatosis
ToxBank Accepted yes
Approved on 20131001



In Vivo Data ? Compound Assessment
Adverse Events ?

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most toxic substances known. TCDD toxicity is associated with activation of the AHR receptor [Kimbrough, 1974; Vickers et al., 1985]. The extreme toxicity of TCDD is partly a function of its very long in vivo half-life of approximately 1 month [Vickers et al., 1985]. It is not metabolized and is protected from excretion by partitioning into tissues, especially the liver and adipose tissue [Birnbaum & Tuomisto, 2000].

β-Naphthoflavone has been selected as an alternative AHR receptor agonist for in vitro studies. It is safer to handle due to its much shorter in vivo half-life, which is on the order of 0.5-1 hr. However, the preponderance of literature on activation of AHR is based on TCDD-dependent effects.

Hyperplastic responses to TCDD are observed primarily in epithelial tissues: gastric mucosa, bladder, and skin. Hepatocellular carcinomas are observed in rats; skin tumors are observed in mice. Other adverse events include chloracne (hyperkeratotic and hyperproliferative responses), hepatic dysfunction, peripheral neuritis, disorders of fat metabolism, and porphyria cutanea tarda. Reproductive capacities are drastically reduced in most species, due primarily to spontaneous abortions. The most sensitive adverse effects observed in multiple species are developmental, including effects on the developing immune, nervous, and reproductive systems [Vickers et al., 1985; Birnbaum & Tuomisto, 2000].

With regards to the liver specifically, TCDD is associated with hyperplasia, fatty infiltration, and necrosis. Altered lipid metabolism leads to changes in serum triglycerides and cholesterol, as well as decreased serum glucose levels. Death from TCDD exposure follows a characteristic wasting syndrome, in which animals mobilize much of their body fat and even protein [Birnbaum & Tuomisto, 2000].

The toxicity of TCDD and other AHR receptor agonists can vary between species by 4 orders of magnitude, which affects the toxicity profile both quantitatively and qualitatively. Humans are one of the species that is least sensitive to TCDD [Carlson et al., 2009; Vickers et al., 1985]. Thus, although the liver is thought to be the target organ most sensitive to dioxins in the rat, comparative EC50’s and evidence in highly exposed humans suggests that human liver is not be a sensitive target organ for AHR-mediated toxicity. Since the skin is the human target organ that is most overtly responsive to dioxin toxicity, it is possible that keratinocytes are more central than hepatocytes to human toxicity [Carlson et al., 2009].

Not all AhR induction is associated with toxicity the pronounced toxicities of the dioxins since many AhR ligands are used as therapeutic agents [Bateman et al., 2003; Loaiza-Perez et al., 2004; Morrow et al., 2004; Simica et al., 2013].

References:

-Bateman, D.N., Colin-Jones, D., Hartz, S., Langman, M., Logan, R.F., Mant, J., Murphy, M., Paterson, K.R., Rowsell, R., Thomas, S., Vessey, M. (2003) “Mortality study of 18 000 patients treated with omeprazole”, Gut 52:942–946
-Linda S. Birnbaum & Jouko Tuomisto, “Non-carcinogenic effects of TCDD in animals”, Food Additives and Contaminants, 17:275-288 (2000).
-Erik A. Carlson, Colin McCulloch, Aruna Koganti, Shirlean B. Goodwin, Thomas R. Sutter, and Jay B. Silkworth, “Divergent Transcriptomic Responses to Aryl Hydrocarbon Receptor Agonists between Rat and Human Primary Hepatocytes”, Toxicological Sciences 112, 257–272 (2009).
-Kimbrough, R. D., “ The toxicity of polychlorinated polycyclic compounds and related chemicals”, CRC Crit. Rev. Toxicol. 2: 445-498 (1974).
-Loaiza-Perez, A.I., Kenney, S., Boswell, J., Hollingshead, M., Alley, M.C., Hose, C., Ciolino, H.P., Yeh, G.C., Trepel, J.B., Vistica, D.T., Sausville, E.A., 2004. “Aryl hydrocarbon receptor activation of an antitumor aminoflavone: basis of selective toxicity for MCF-7 breast tumor cells” Mol. Cancer Ther. 3:715–725.
-Morrow, D., Qin, C., Smith 3rd, R., Safe, S., 2004. “Aryl hydrocarbon receptor-mediated inhibition of LNCaP prostate cancer cell growth and hormone-induced transactivation”, J. Steroid Biochem. Mol. Biol. 88:27–36.
-Damir Simica, Cathy Eulera, Emily Hainesa, Aiqing Heb, W. Mike Pedena, R. Todd Buncha, Thomas Sandersona, Terry Van Vleeta, “MicroRNA changes associated with atypical CYP1A1 inducer BMS-764459”, Toxicology 311 (2013) 169– 177.
-Alison E. M. Vickers, Tracy C. Sloop and George W. Lucier, “Mechanism of Action of Toxic Halogenated Aromatics”,Environmental Health Perspectives 59:121-128 (1985).
Toxicity Mechanisms ?

β-Naphthoflavone is a pure agonist of AHR (aryl hydrocarbon receptor). AHR is a transcription factor that is not a member of the nuclear hormone family but functions similarly. In the absence of ligand, it is found bound to a dimer of 90-kDa heat shock protein and the cochaperone X-associated protein 2 [Petrulis and Perdew, 2002]. After binding a ligand, the AHR complex translocates into the nucleus, where ARNT (aryl hydrocarbon receptor nuclear translocator) displaces 90-kDa heat shock protein/X-associated protein 2 and heterodimerizes with AHR. The AHR/ARNT heterodimer is capable of binding to a dioxin-response element (DRE), which can mediate changes in gene transcription.

Historically, the AHR target genes that have been most often studied are involved in phase I xenobiotic metabolism, for example via activation of CYP1A1 and CYP1B1. However, an expanding list of AHR target genes involved in a wide range of pathways is emerging. [Murray et al., 2011; Beischlag et al., 2008].

Studies of transgenic mice with a mutant AHR that does not bind DRE have identified AHR-regulated processes that are not mediated via DRE. Thus β-naphthoflavone shows AHR-dependent, DRE-independent repression of cholesterol biosynthesis in mice and primary human hepatocytes. Current evidence suggests that this effect represents repression of a constitutive role of AHR in cholesterol biosynthesis and appears to be directly or indirectly (via cofactor recruitment) mediated via repression of SREBP2 [Tanos et al., 2012]. The fact that AHR also regulates expression of CAR and FXR suggests a coordinated regulation of lipid metabolism via AHR and these two nuclear hormone receptors plus PXR and PPARγ [Fletcher et al., 2005; Patel et al., 2007; He et al., 2011]. These results are consistent with the observation that exposure to TCDD causes disruption of lipid metabolism (but elevation of cholesterol) in humans [Pelclova et al., 2002].

Conversely, AHR agonists or constitutively active AhR mutants cause steatosis, which is not mediated by SREBP-1c and up regulation of fatty acid synthesis (consistent with the repression of SREBP2 and repression of cholesterol synthesis) but rather by activation of CD36 and increased uptake of fatty acids into the liver [Xie et al., 2011].

In addition, structure-activity studies have identified an AHR agonist, 3’,4’-dimethoxy-α-naphthoflavone, that depresses the acute-phase inflammatory response, including suppression of complement factor C3, independent of the DRE [Murray et al., 2011].

GNF351 can be used as a pure antagonist of both DRE-dependent and DRE-independent activities with no partial agonist activity [Smith et al., 2011, DiNatale et al., 2012].

References:

-

Beischlag TV, Luis Morales J, Hollingshead BD, and Perdew GH (2008) “The aryl hydrocarbon receptor complex and the control of gene expression. Crit Rev Eukaryot Gene Expr 18:207–250.

-

Erik A. Carlson, Colin McCulloch, Aruna Koganti, Shirlean B. Goodwin, Thomas R. Sutter, and Jay B. Silkworth, “Divergent Transcriptomic Responses to Aryl Hydrocarbon Receptor Agonists between Rat and Human Primary Hepatocytes”, Toxicological Sciences 112, 257–272 (2009).

-

Brett C. DiNatale, Kayla Smith, Kaarthik John, Gowdahalli Krishnegowda, Shantu G. Amin, and Gary H. Perdew, “Ah Receptor Antagonism Represses Head and Neck Tumor Cell Aggressive Phenotype”, Mol Cancer Res (2012) 10:1369-1379.

-

Fletcher N, Wahlstrom D, Lundberg R, Nilsson CB, Nilsson KC, Stockling K, Hellmold H, Hakansson H., “2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alters the mRNA expression of critical genes associated with cholesterol metabolism, bile acid biosynthesis, and bile transport in rat liver: a microarray study”, Toxicol Appl Pharmacol. (2005) 207:1–24.

-

Jinhan He, Jung Hoon Lee, Maria Febbraio and Wen Xie, “The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon receptor in fatty liver dise”, Experimental Biology and Medicine (2011) 236:1116-1121.

-

Iain A. Murray, Colin A. Flaveny, Christopher R. Chiaro, Arun K. Sharma, Rachel S. Tanos, Jennifer C. Schroeder, Shantu G. Amin, William H. Bisson, Siva K. Kolluri, and Gary H. Perdew, “Suppression of Cytokine-Mediated Complement Factor Gene Expression through Selective Activation of the Ah Receptor with 3’,4’-Dimethoxy-α-naphthoflavone”, Mol Pharmacol 79:508–519 (2011).

-

Patel RD, Hollingshead BD, Omiecinski CJ, Perdew GH, “Aryl-hydrocarbon receptor activation regulates constitutive androstane receptor levels in murine and human liver”, Hepatology (2007) 46:209–218.

-

Pelclova D, Fenclova Z, Preiss J, Prochazka B, Spacil J, Dubska Z, Okrouhlik B, Lukas E, Urban P, “Lipid metabolism and neuropsychological follow-up study of workers exposed to 2,3,7,8-tetrachlordibenzo- p-dioxin”, Int Arch Occup Environ Health, (2002) 75(Suppl):S60–S66.

-

Petrulis JR and Perdew GH (2002) “The role of chaperone proteins in the aryl hydrocarbon receptor core complex”, Chem Biol Interact 141:25–40.

-

Kayla J. Smith, Iain A. Murray, Rachel Tanos, John Tellew, Anthony E. Boitano, William H. Bisson, Siva K. Kolluri, Michael P. Cooke, and Gary H. Perdew, “Identification of a High-Affinity Ligand That Exhibits Complete Aryl Hydrocarbon Receptor Antagonism”, J Pharmacol Exp Ther. 338:318–327 (2011).

-

Rachel Tanos, Rushang D. Patel, Iain A. Murray, Philip B. Smith, and Gary H. Perdew, “Ah receptor regulates the cholesterol biosynthetic pathway in a dioxin response element-independent manner”, Hepatology (2012 ) 55:1994–2004.

Therapeutic Target ? Not Applicable

PubMed references

The following resource link will perform a PubMed query for the terms " Beta-Naphthoflavone " and "liver toxicity".
Beta-Naphthoflavone Search

PK-ADME ? Compound Assessment
PK parameters ? PK data for humans was not found. In the rat, single iv bolus gave PK parameters:
CL130 mL/min/kg
Vd6 L/kg
t1/240 min

Clearance appears to be solely via metabolism since no unchanged parent compound is found in the urine. The rate of clearance approaches the rate of hepatic blood flow. The t½ decreased to 27 min after prolonged infusion, indicating that the compound induces its own metabolism [Adedoyin et al., 1993].

References:

-Adedayo Adedoyin, Leon Aarons, and J Brian Houston, “Time-Dependent Disposition of Β-Naphthoflavone in the Rat”, Pharm. Res. 10:35-43 (1993).
Therapeutic window ? Not Applicable
Metabolically activated ? No

Omics and IC50 Data ? Compound Assessment
Gene expression profiles known. ? Induction of CYP1A isozymes is a sensitive indicator for AHR activation. Induction of CYP1A1 is seen in diverse tissues in many species, while that of CYP1A2 is restricted to the liver [Birnbaum & Tuomisto, 2000].

β-Naphthoflavone is a reference standard for induction of CYP1A2 [Gerets et al., 2012]. An average 10-fold increase in CYP1A2 activity was observed in the cited experiment. Induction of CYP1A2 was observed equally in HepG2, HepaRG and primary human hepatocytes, which Gerets et al. attribute to the ubiquitous expression of AHR in many immortalized cell lines. Cell lines may be preferable to primary hepatocytes in this regard since there was high donor-to-donor variability (4-fold) for gene expression in the latter.

Gene expression profiles for AHR ligands vary greatly between species, between strains of a single species, and between in vitro and in vivo dosing for a given strain [Carlson et al., 2009]. The strain/species variability is due to variability in the sequence of the ligand binding domain, variability in core DRE (dioxin response element) sequences, and variability in the ability to recruit coactivator proteins. While gene expression patterns vary widely between mouse and rat, the major toxicities are the same, indicating that the toxicities are associated with a relatively limited number of genes. Variability between in vitro and in vivo gene expression patterns is attributed in some cases to cell culture artifacts; secondary in vivo responses well downstream of primary AHR signaling; and the more complex mix of cells in tissues vs. cultured cells. Additional studies of variability have been reviewed by Walker (2007). This complexity recommends that the goal in developing predictive in vitro models should be to detect specific markers of AHR activation rather than more generic indicators such as cell viability or changes in lipid metabolism. Increased expression of CYP1A1 and/or CYP1A2 is a diagnostic marker for both classical DRE-dependent and “atypical” AHR activation [Simica et al., 2013]. Suppression of complement factor C3 is indicative, but not necessarily uniquely so, of nonDRE-dependent suppression of inflammation [Murray et al., 2011].

AHR agonists modulate the inflammatory response in multiple tissues. This includes DRE-independent suppression of complement factor C3 release from the liver and CD55 in host cells, which protects the host cells from complement-dependent lysis [Murray et al., 2011; Narayanan, et al., 2012 ].

In cell lines derived by differentiation of stem cells it is relevant that AHR influences expansion of human hematopoietic stem cells in cell culture. [Boitano et al., 2010].

Gene expression in mouse liver in response to β-naphthoflavone is reported by [Patel et al., 2007] and with comparison to other AHR agonists by [Nault et al., 2013]. Gene expression in human hepatocytes in a screening real-time PCR assay is reported by [Nishimura et al., 2009] and with comparison to agonists of nuclear hormone receptors by [Gerets et al., 2012]. A review of gene expression profiles is provided by [Beischlag et al., 2008; Woods et al., 2007].

Studies of miRNA expression in response to AHR ligands are beginning to appear and can be diagnostic of activation [Simica et al., 2013]. The effect of miRNA in modulation of the overall response to agonists is not yet fully understood.

References:

-

Beischlag TV, Luis Morales J, Hollingshead BD, and Perdew GH (2008) “The aryl hydrocarbon receptor complex and the control of gene expression. Crit Rev Eukaryot Gene Expr 18:207–250.

-

Linda S. Birnbaum & Jouko Tuomisto, “Non-carcinogenic effects of TCDD in animals”, Food Additives and Contaminants, 17:275-288 (2000).

-

Boitano AE, Wang J, Romeo R, Bouchez LC, Parker AE, Sutton SE, Walker JR, Flaveny CA, Perdew GH, Denison MS, et al. (2010) “Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells”, Science 329:1345–1348.

-

Erik A. Carlson, Colin McCulloch, Aruna Koganti, Shirlean B. Goodwin, Thomas R. Sutter, and Jay B. Silkworth, “Divergent Transcriptomic Responses to Aryl Hydrocarbon Receptor Agonists between Rat and Human Primary Hepatocytes”, Toxicological Sciences 112, 257–272 (2009).

-

H. H. J. Gerets, K. Tilmant, B. Gerin, H. Chanteux, B. O. Depelchin, S. Dhalluin, F. A. Atienzar, “Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins”, Cell Biol Toxicol (2012) 28:69–87.

-

Iain A. Murray, Colin A. Flaveny, Christopher R. Chiaro, Arun K. Sharma, Rachel S. Tanos, Jennifer C. Schroeder, Shantu G. Amin, William H. Bisson, Siva K. Kolluri, and Gary H. Perdew, “Suppression of Cytokine-Mediated Complement Factor Gene Expression through Selective Activation of the Ah Receptor with 3’,4’-Dimethoxy-α-naphthoflavone”, Mol Pharmacol 79:508–519 (2011).

-

Gitanjali A. Narayanan, Iain A. Murray, Gowdahalli Krishnegowda, Shantu Amin and Gary H. Perdew (2012) “Selective Ah receptor modulator mediated repression of CD55 expression induced by cytokine exposure”, J Pharmacol Exp Ther 342(2):345-355.

-

Rance Naulta, Agnes L. Forgacsa, Edward Derea, Timothy R. Zacharewski, “Comparisons of differential gene expression elicited by TCDD, PCB126, βNF, or ICZ in mouse hepatoma Hepa1c1c7 cells and C57BL/6 mouse liver”, Toxicology Letters, Available online 29 August 2013.

-

Nishimura M, Narimatsu S, and Naito S. “Evaluation of induction potency of new drug candidates on CYP1A2 and CYP3A4 using real-time one-step RT-PCR in primary cultures of cryopreserved human hepatocytes”, Drug Metab Pharmacokinet. 2009;24(5):446-50.

-

Patel RD, Hollingshead BD, Omiecinski CJ, Perdew GH, “Aryl-hydrocarbon receptor activation regulates constitutive androstane receptor levels in murine and human liver”, Hepatology (2007) 46:209–218.

-

Damir Simica, Cathy Eulera, Emily Hainesa, Aiqing Heb, W. Mike Pedena, R. Todd Buncha, Thomas Sandersona, Terry Van Vleeta, “MicroRNA changes associated with atypical CYP1A1 inducer BMS-764459”, Toxicology 311 (2013) 169– 177

-

Nigel J. Walker “Toxicological Highlight: Unraveling the Complexities of the Mechanism of Action of Dioxins”, Toxicological Sciences 95(2), 297–299 (2007).

-

Courtney G. Woods, John P. Vanden Heuvel, and Ivan Rusyn, “Genomic Profiling in Nuclear Receptor-Mediated Toxicity”, Toxicologic Pathology, 35:474–494, 2007.

Proteomics profiles known. ?
Metabonomics profiles known. ?
Fluxomics profiles known. ?
Epigenomics profiles known. ?
Observed IC50 for in vitro cellular efficacy. ? Not Applicable
Observed IC50 for in vitro cellular toxicity studies. ? Of the compounds in a ToxCast high throughput screen for nuclear hormone ligands, 18% were agonists for AHR [Martin et al., 2010]. There is a high probability, therefore, that an unknown compound in a toxicity screen may be a ligand for this receptor. The AhR binding pocket accommodates hydrophobic aromatic compounds that contain at least two aromatic rings and can adopt a planar confirmation [Safe, 1995; Gu et al., 2012].

Conditions for measuring gene expression profiles:

  • 25 uM β-naphthoflavone, gene expression measured at 24 h, CYP activity measured at 72 h [Gerets et al., 2012]
  • 25 uM β-naphthoflavone, gene expression measured at 48 h [Nishimura et al., 2009]

EC50’s for dioxins and polychlorinated biphenyls (but not β-naphthoflavone) in hepatocytes from multiple species are provided by Carlson et al. (2009). Data in this reference supports an extensive discussion of interspecies variability in responses to AHR ligands.

References:

-

Erik A. Carlson, Colin McCulloch, Aruna Koganti, Shirlean B. Goodwin, Thomas R. Sutter, and Jay B. Silkworth, “Divergent Transcriptomic Responses to Aryl Hydrocarbon Receptor Agonists between Rat and Human Primary Hepatocytes”, Toxicological Sciences 112, 257–272 (2009).

-

H. H. J. Gerets, K. Tilmant, B. Gerin, H. Chanteux, B. O. Depelchin, S. Dhalluin, F. A. Atienzar, “Characterization of primary human hepatocytes, HepG2 cells, and HepaRG cells at the mRNA level and CYP activity in response to inducers and their predictivity for the detection of human hepatotoxins”, Cell Biol Toxicol (2012) 28:69–87.

-

Chenggang Gu, Mohammad Goodarzi, Xinglun Yang, Yongrong Bian, Cheng Sun, Xin Jiang, “Predictive insight into the relationship between AhR binding property and toxicity of polybrominated diphenyl ethers by PLS-derived QSAR”, Toxicology Letters 208 (2012) 269– 274.

-

Matthew T. Martin, David J. Dix, Richard S. Judson, Robert J. Kavlock, David M. Reif, Ann M. Richard, Daniel M. Rotroff, Sergei Romanov, Alexander Medvedev, Natalia Poltoratskaya, Maria Gambarian, Matt Moeser, Sergei S. Makarov, and Keith A. Houck (2010) “Impact of Environmental Chemicals on Key Transcription Regulators and Correlation to Toxicity End Points within EPA’s ToxCast Program”, Chem. Res. Toxicol. 23:578–590.

-

Nishimura M, Narimatsu S, and Naito S. “Evaluation of induction potency of new drug candidates on CYP1A2 and CYP3A4 using real-time one-step RT-PCR in primary cultures of cryopreserved human hepatocytes”, Drug Metab Pharmacokinet. 2009;24(5):446-50.

-

Safe, S.H. (1995) “Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds”, Pharmacol. Ther. 67:247–281.

Physical Properties ? Compound Assessment
Accepted and listed within the ToxCast/Tox21 program. ? No - Not included in ToxCast Phase I and II Chemicals List
Substance stability. ? Stable under recommended storage conditions Santa Cruz Biotech
Soluble in buffer solution at 30 times the in vitro IC50 for toxicity. ? Aqueous solubility in phosphate buffer (pH 7.4) : <0.15 µg/mL [Fujita Y, Yonehara M, Tetsuhashi M, Noguchi-Yachide T, Hashimoto Y, Ishikawa M. β-Naphthoflavone analogs as potent and soluble aryl hydrocarbon receptor agonists: Improvement of solubility by disruption of molecular planarity. Bioorganic & Medicinal Chemistry 18 (2010) 1194–1203]

Estimated water solubility: 1.77 mg/L (25°C) [Meylan, WM et al. (1996) from SRC PhysProp Database]


estimated intrinsic solubility : 6.8493E-4 mg/ml
estimated solubility in pure water at pH 7: 6.8493E-4 mg/ml
estimated solubility in water at pH 7.4: 6.8493E-4 mg/ml
Calculations performed using ACD/PhysChem v12.02

Solubility in DMSO 100 times buffer solubility. ? Slightly soluble in DMSO Santa Cruz Biotech
Vessel binding properties. ?
Vapor pressure. (Non-volatile) ? estimated vapor pressure (25°C): 5.48E-08 mmHg (Calculation performed using EPI Suite v4.10)

Calculated/Predicted Properties

Water Solubility Results
pH Sol, mg/ml Flags  % Graph
0.0 6.85E-4 N 100 Beta-naphthoflavone solubility.png
0.1 6.85E-4 N 100
0.2 6.85E-4 N 100
0.3 6.85E-4 N 100
0.4 6.85E-4 N 100
0.5 6.85E-4 N 100
0.6 6.85E-4 N 100
0.7 6.85E-4 N 100
0.8 6.85E-4 N 100
Summary Solubility Data
Intrinsic Solubility, mg/ml 6.8493E-4
Intrinsic Solubility, log(S, mol/l) -5.5994
Solubility in Pure Water @pH = 7, mg/ml 6.8493E-4
Calculations performed using ACD/PhysChem v 12.02
LogD Results
pH LogD pH LogD Graph
0.0 5 0.9 5 Beta-naphthoflavone logd.png
0.1 5 1.0 5
0.2 5 1.1 5
0.3 5 1.2 5
0.4 5 1.3 5
0.5 5 1.4 5
0.6 5 1.5 5
0.7 5 1.6 5
0.8 5 1.7 5
Calculations performed using ACD/PhysChem v 12.02
Single-valued Properties
Property Value Units Error
LogP 5 0.27
MW 272.3 -
PSA 26.3 -
FRB 1 -
HDonors 0 -
HAcceptors 2 -
Rule Of 5 1 -
Molar Refractivity 82.05 cm3 0.3
Molar Volume 213.39 cm3 3
Parachor 580.65 cm3 6
Index of Refraction 1.7 0.02
Surface Tension 54.82 dyne/cm 3
Density 1.28 g/cm3 0.06
Polarizability 32.53 10E-24 cm3 0.5
Boiling Point 460.94 °C 45
Calculations performed using ACD/PhysChem v 12.02
Property Name Value Units Source
Estimated VP 5.48E-08 mm Hg EPI Suite v4.10
Estimated VP 7.31E-06 Pa EPI Suite v4.10
Estimated Water Solubility 1.772 mg/L EPI Suite v4.10
WATERNT Frag Water Solubility Estimate 0.071637 mg/L EPI Suite v4.10






Authors of this ToxBank wiki page

David Bower
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