DIOSMETIN

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H12O6
Molecular Weight	300.2629
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(C=C1O)C2=CC(=O)C3=C(O2)C=C(O)C=C3O

InChI

InChIKey=MBNGWHIJMBWFHU-UHFFFAOYSA-N

InChI=1S/C16H12O6/c1-21-13-3-2-8(4-10(13)18)14-7-12(20)16-11(19)5-9(17)6-15(16)22-14/h2-7,17-19H,1H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27725131 | https://www.ncbi.nlm.nih.gov/pubmed/28835383 | https://www.ncbi.nlm.nih.gov/pubmed/24092244

Diosmetin is the aglycone of the flavonoid glycoside diosmin, which occurs naturally in citrus fruits. Diosmetin is found in the legume Acacia farnesiana Wild and Olea europaea L. leaves. Diosmin is hydrolyzed to its aglycone diosmetin by intestinal microflora enzymes before its absorption into the body. Pharmacologically, diosmetin is reported to exhibit anticancer, antimicrobial, antioxidant, oestrogenic and anti-inflammatory activities. Diosmetin increased inhibitory GSK-3beta phosphorylation, while selectively reducing gamma-secretase activity, Abetta generation, tau hyperphosphorylation and pro-inflammatory activation of microglia in vitro, without altering Notch processing. Therefore, diosmetin could be considered as potential candidate for novel anti- Alzheimer's disease therapy. Diosmetin is ER-beta agonist and potential novel drug for the acute myeloid leukemia treatment.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cytochrome P450 1A1 31 Target ID: CHEMBL2231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20696580	Inhibitor 8297	140.0 nM [IC50]
Cytochrome P450 1A2 72 Target ID: CHEMBL3356 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20696580	Inhibitor 8297	2.4 µM [IC50]
Cytochrome P450 1B1 4 Target ID: CHEMBL4878 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20696580	Inhibitor 8297	29.0 nM [IC50]
Estrogen receptor beta 110 Target ID: CHEMBL242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28835383	Agonist 2678
NF-kappa B signaling pathway 84 Target ID: map04064 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28101238	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Acute myeloid leukemia 136 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28835383	Primary	Preclinical	Unknown Approved Use Unknown
Hepatocellular carcinoma 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28101238	Preventing	Basic research	Unknown Approved Use Unknown
Alzheimer’s disease 272 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27725131	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Resistance of MCF-7 cells to dimethylbenz(a)anthracene-induced apoptosis is due to reduced CYP1A1 expression.	2002 Aug	12118336
A benzoquinone and flavonoids from Cyperus alopecuroides.	2002 Jun	12031430
Induction of human UDP-glucuronosyltransferase UGT1A1 by flavonoids-structural requirements.	2002 May	11950788
Structural requirements of flavonoids for inhibition of antigen-Induced degranulation, TNF-alpha and IL-4 production from RBL-2H3 cells.	2002 Oct	12150856
DNA damage and cell cycle arrest induced by 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203, NSC 703786) is attenuated in aryl hydrocarbon receptor deficient MCF-7 cells.	2003 Feb 24	12592376
Degradation of flavonoid aglycones by rabbit, rat and human fecal flora.	2003 May	12736527
Structural requirements of flavonoids for nitric oxide production inhibitory activity and mechanism of action.	2003 May 1	12670650
The beta-D-glucoside and sodium-dependent glucose transporter 1 (SGLT1)-inhibitor phloridzin is transported by both SGLT1 and multidrug resistance-associated proteins 1/2.	2003 Nov	14570756
Free radical scavenging abilities of flavonoids as mechanism of protection against mutagenicity induced by tert-butyl hydroperoxide or cumene hydroperoxide in Salmonella typhimurium TA102.	2003 Sep 9	12972054
A validated HPLC determination of the flavone aglycone diosmetin in human plasma.	2004 Dec	15386576
Metabolism of apigenin by rat liver phase I and phase ii enzymes and by isolated perfused rat liver.	2004 Jan	14709621
Effect of the rootstock and interstock grafted in lemon tree (Citrus limon (L.) Burm.) on the flavonoid content of lemon juice.	2004 Jan 28	14733516
Antitubercular constituents of Valeriana laxiflora.	2004 Jun	15229801
Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships.	2004 Nov 15	15476679
[Investigation of the hepatoprotector action of natural flavonoids].	2004 Nov-Dec	15707014
Flavonoid glycosides inhibit oral cancer cell proliferation--role of cellular uptake and hydrolysis to the aglycones.	2005 Aug	16102260
Analysis and quantification of flavonoidic compounds from Portuguese olive (Olea europaea L.) leaf cultivars.	2005 Feb	15715265
Quantitative structure activity relationship studies on the flavonoid mediated inhibition of multidrug resistance proteins 1 and 2.	2005 Feb 15	15670588
In vitro antioxidant activity of some Teucrium species (Lamiaceae).	2005 Jun	16179134
Determination of active components in rosemary by capillary electrophoresis with electrochemical detection.	2005 Sep 15	15925471
The efflux of flavonoids morin, isorhamnetin-3-O-rutinoside and diosmetin-7-O-beta-D-xylopyranosyl-(1-6) -beta-D-glucopyranoside in the human intestinal cell line caco-2.	2006 Aug	16832612
Polar constituents from the aerial parts of Origanum vulgare L. Ssp. hirtum growing wild in Greece.	2006 Jul 26	16848522
Flavonoid glycosides in bergamot juice (Citrus bergamia Risso).	2006 May 31	16719517
Anti-proliferative and antioxidant constituents from Tecoma stans.	2006 Nov-Dec	17294687
Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: analysis of the structure-activity relationship.	2006 Oct 16	16934226
Raddeanalin, a new flavonoid glycoside from the leaves of Salix raddeana Laksh.	2007 Apr-Aug	17701556
Complete assignments of NMR data of 13 hydroxymethoxyflavones.	2007 Dec	17987643
A new flavone glycoside from the fruits of Luffa cylindrica.	2007 Dec	17689887
Flavonoids modulate monocarboxylate transporter-1-mediated transport of gamma-hydroxybutyrate in vitro and in vivo.	2007 Feb	17108059
Pensteminoside, an unusual catalpol-type iridoid from Penstemon gentianoides HBK (Plantaginaceae).	2007 Jul	17507063
Plant-derived polyphenols attenuate lipopolysaccharide-induced nitric oxide and tumour necrosis factor production in murine microglia and macrophages.	2008 Apr	18186104
Prediction of intestinal absorption and metabolism of pharmacologically active flavones and flavanones.	2008 Apr 1	18249545
Effect of flavonoids on rat splenocytes, a structure-activity relationship study.	2008 Aug 15	18590707
Different flavonoids present in the micronized purified flavonoid fraction (Daflon 500 mg) contribute to its anti-hyperpermeability effect in the hamster cheek pouch microcirculation.	2008 Feb	18277344
New features on the fragmentation and differentiation of C-glycosidic flavone isomers by positive electrospray ionization and triple quadrupole mass spectrometry.	2008 Jun	18470889
Flavonoids diosmetin and luteolin inhibit midazolam metabolism by human liver microsomes and recombinant CYP 3A4 and CYP3A5 enzymes.	2008 Mar 15	18191104
Acasiane A and B and farnesirane A and B, diterpene derivatives from the roots of Acacia farnesiana.	2009 Feb	19101886
Aurintricarboxylic acid inhibits influenza virus neuraminidase.	2009 Feb	19014974
Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention.	2009 Jun 16	19531241
[Chemical constituents of Galium verum].	2009 Nov	20209910
Flavonoids diosmetin and hesperetin are potent inhibitors of cytochrome P450 2C9-mediated drug metabolism in vitro.	2010	20877134

Patents

Sample Use Guides

In Vivo Use Guide

Mice: 50mg /kg/every other day for 6 weeks

Route of Administration: Intraperitoneal

In Vitro Use Guide

Diosmetin caused G1 arrest at 10 microM in MDA-MB 468 cells after 48-h treatment whereas this effect was not observed in MCF-10A cells.

Name

Type

Language

DIOSMETIN

Official Name

English

4'-METHYLLUTEOLIN

Common Name

English

4H-1-BENZOPYRAN-4-ONE, 5,7-DIHYDROXY-2-(3-HYDROXY-4-METHOXYPHENYL)-

Systematic Name

English

3',5,7-TRIHYDROXY-4'-METHOXYFLAVONE

Systematic Name

English

DIOSMETIN [INCI]

Common Name

English

DIOSMETIN [MI]

Common Name

English

5,7-DIHYDROXY-2-(3-HYDROXY-4-METHOXYPHENYL)CHROMEN-4-ONE

Systematic Name

English

DIOSMETINE

Common Name

English

LUTEOLIN-4'-METHYL ETHER

Common Name

English

CYANIDENON-4'-METHYL ETHER 1479

Common Name

English

DIOSMETOL

Common Name

English

Diosmetin [WHO-DD]

Common Name

English

5,7-DIHYDROXY-2-(3-HYDROXY-4-METHOXYPHENYL)-4H-1-BENZOPYRAN-4-ONE

Systematic Name

English

FLAVONE, 3',5,7-TRIHYDROXY-4'-METHOXY-

Systematic Name

English

Classification Tree Code System Code

DSLD

4156 (Number of products:7)