38183-03-8 Usage
Description
7,8-Dihydroxyflavone (7,8-DHF) is a naturally occurring flavone derived from the tree Godmania aesculifolia. It is a selective tyrosine kinase receptor B (TrkB) agonist with neurotrophic effects in various neurological diseases such as stroke and Parkinson's disease. 7,8-DHF exhibits neuroprotective and neuroregenerative properties by binding to TrkB receptors, similar to brain-derived neurotrophic factor (BDNF). This interaction promotes the growth of dendrites and restores communication between neurons in animal models. It is a white crystalline powder or yellow solid, soluble in methanol, ethanol, DMSO, and other organic solvents.
Uses
Used in Pharmaceutical Industry:
7,8-Dihydroxyflavone is used as a small-molecule TrkB agonist for its neurotrophic effects in treating neurological disorders. It has demonstrated the ability to reverse memory deficits and BACE1 elevation in a mouse model of Alzheimer's disease, making it a potential therapeutic option for Alzheimer's, as well as other neurological disorders such as Rett syndrome and PTSD.
Used in Neurotoxicology Research:
7,8-Dihydroxyflavone is used as a counteracting agent against the inhibition of NMDA receptors caused by lead poisoning. It has been shown to confer protective effects in live rats, highlighting its potential application in neurotoxicology research and treatment.
Used in Drug Development:
Due to its neuroprotective and neuroregenerative properties, 7,8-Dihydroxyflavone is used as a starting point for the development of new drugs targeting neurological disorders. Its ability to promote dendrite growth and restore neuronal communication makes it a promising candidate for further research and potential therapeutic applications.
Biological Activity
7,8-Dihydroxyflavone (7,8-DHF) is a monophenolic flavone with diverse effects. It acts as an agonist of the neurotrophic tyrosine kinase receptor TrkB (Kd = 320 nM), protecting neurons that express TrkB from apoptosis. 7,8-DHF is neuroprotective in an animal model of Parkinson’s disease. It supports emotional learning in mice and reverses memory deficits in a mouse model of Alzheimer’s disease. It also improves motor function and extends survival in an animal model of Huntington’s disease. 7,8-DHF inhibits the cytochrome P450 aromatase (IC50 = 10 μM) and, in this way, alters estrogen metabolism. It also has antioxidant action that increases intracellular glutathione synthesis and scavenges reactive oxygen species.
Biochem/physiol Actions
7,8-Dihydroxyflavone is a selective tyrosine kinase receptor B (TrkB) receptor agonist. It manifests all the therapeutic effects of brain-derived neurotrophic factor (BDNF)—such as protecting neurons from apoptosis, inhibiting kainic acid-induced toxicity, decreasing infarct volumes in stroke, and neuroprotecting in an animal model of Parkinson′s disease—without the poor pharmacokinetic profile of BDNF limiting its therapeutic potential.
Side effects
As with any other drug, 7,8-DHF is not without its side effects. However, there are not as many side effects associated with the use of 7,8-DHF as it is a natural product.The following are some reported side effects associated with the use of 7,8-DHF or products that contain it:OverstimulationRestlessnessDizzinessNauseaIrritabilityTrouble sleeping
Mode of action
7,8-Dihydroxyflavone (7,8-DHF, tropoflavin) is the most common and effective flavone identified in Sophora plants.7,8-DHF mimics the effects of brain-derived neurotrophic factor (BDNF) in brain cells by activating tropomyosin-related kinase B (TrkB) receptors, the typical target of BDNF.The therapeutic potential of BDNF is restricted due to its short half-life (less than 10 minutes) and its inability to cross the blood-brain barrier because of its large size. Unlike BDNF 7,8-DHF is able to penetrate the blood-brain barrier and enter the central nervous system (CNS) .7,8-DHF also increases the production of Nrf2. Nrf2 increases antioxidants enzymes such as heme oxygenase 1 (HO-1) and also enzymes that repair DNA (8-oxoguanine DNA glycosylase-1 – OGG1) .
References
1) Jang et al. (2010), A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone; Proc. Natl. Acad. Sci. USA, 107 2687
2) Liu et al. (2014) Biochemical and biophysical investigation of the brain-derived neurotrophic factor mimetic 7,8-dihydroxyflavone in the binding and activation of the TrkB receptor; J. Biol. Chem., 289 27571
3) Jiang et al. (2013) Small-molecule TrkB receptor agonist improve motor function and extend survival in a mouse model of Huntington’s disease; Hum. Mol. Genet., 22 2462
4) Zhao et al. (2016) Post-injury Treatment of 7,8-Dihydroxyflavone Promotes Neurogenesis in the Hippocampus of the Adult Mouse; J. Neurotrauma, 33 2055
5) Korkmaz et al. (2014) 7,8-dihydroxyflavone improves motor performance and enhances lower motor neuronal survival in a mouse model of amyotrophic lateral sclerosis; Neurosci. Lett., 566 286
Check Digit Verification of cas no
The CAS Registry Mumber 38183-03-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,8,1,8 and 3 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 38183-03:
(7*3)+(6*8)+(5*1)+(4*8)+(3*3)+(2*0)+(1*3)=118
118 % 10 = 8
So 38183-03-8 is a valid CAS Registry Number.
InChI:InChI=1/C15H10O4/c16-11-7-6-10-12(17)8-13(19-15(10)14(11)18)9-4-2-1-3-5-9/h1-8,16,18H
38183-03-8Relevant articles and documents
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Seka,Prosche
, p. 284,291 (1936)
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Novel synthesised flavone derivatives provide significant insight into the structural features required for enhanced anti-proliferative activity
Ravishankar, Divyashree,Watson, Kimberly A.,Greco, Francesca,Osborn, Helen M. I.
, p. 64544 - 64556 (2016/07/21)
With many cancers showing resistance to current chemotherapies, the search for novel anti-cancer agents is attracting considerable attention. Natural flavonoids have been identified as useful leads in such programmes. However, since an in-depth understanding of the structural requirements for optimum activity is generally lacking, further research is required before the full potential of flavonoids as anti-proliferative agents can be realised. Herein a broad library of 76 methoxy and hydroxy flavones, and their 4-thio analogues, was constructed and their structure-activity relationships for anti-proliferative activity against the breast cancer cell lines MCF-7 (ER +ve), MCF-7/DX (ER +ve, anthracycline resistant) and MDA-MB-231 (ER -ve) were probed. Within this library, 42 compounds were novel, and all compounds were afforded in good yields and >95% purity. The most promising lead compounds, specifically the novel hydroxy 4-thioflavones 15f and 16f, were further evaluated for their anti-proliferative activities against a broader range of cancer cell lines by the National Cancer Institute (NCI), USA and displayed significant growth inhibition profiles (e.g. compound-15f: MCF-7 (GI50 = 0.18 μM), T-47D (GI50 = 0.03 μM) and MDA-MB-468 (GI50 = 0.47 μM) and compound-16f: MCF-7 (GI50 = 1.46 μM), T-47D (GI50 = 1.27 μM) and MDA-MB-231 (GI50 = 1.81 μM)). Overall, 15f and 16f exhibited 7-46 fold greater anti-proliferative potency than the natural flavone chrysin (2d). A systematic structure-activity relationship study against the breast cancer cell lines highlighted that free hydroxyl groups and the B-ring phenyl groups were essential for enhanced anti-proliferative activities. Substitution of the 4-CO functionality with a 4-CS functionality, and incorporation of electron withdrawing groups at C-4′ of the B-ring phenyl, also enhanced activity. Molecular docking and mechanistic studies suggest that the anti-proliferative effects of flavones 15f and 16f are mediated via ER-independent cleavage of PARP and downregulation of GSK-3β for MCF-7 and MCF-7/DX cell lines. For the MDA-MB-231 cell line, restoration of the wild-type p53 DNA binding activity of mutant p53 tumour suppressor gene was indicated.
Antimalarial activity of HIV-1 protease inhibitor in chromone series
Lerdsirisuk, Pradith,Maicheen, Chirattikan,Ungwitayatorn, Jiraporn
, p. 142 - 147 (2015/02/05)
Increasing parasite resistance to nearly all available antimalarial drugs becomes a serious problem to human health and necessitates the need to continue the search for new effective drugs. Recent studies have shown that clinically utilized HIV-1 protease (HIV-1 PR) inhibitors can inhibit the in vitro and in vivo growth of Plasmodium falciparum. In this study, a series of chromone derivatives possessing HIV-1 PR inhibitory activity has been tested for antimalarial activity against P. falciparum (K1 multi-drug resistant strain). Chromone 15, the potent HIV-1 PR inhibitor (IC50 = 0.65 μM), was found to be the most potent antimalarial compound with IC50 = 0.95 μM while primaquine and tafenoquine showed IC50 = 2.41 and 1.95 μM, respectively. Molecular docking study of chromone compounds against plasmepsin II, an aspartic protease enzyme important in hemoglobin degradation, revealed that chromone 15 exhibited the higher binding affinity (binding energy = -13.24 kcal/mol) than the known PM II inhibitors. Thus, HIV-1 PR inhibitor in chromone series has the potential to be a new class of antimalarial agent.