DIHYDROMETHYSTICIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C15H16O5
Molecular Weight	276.2845
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(=O)O[C@@H](CCC2=CC3=C(OCO3)C=C2)C1

InChI

InChIKey=RSIWXFIBHXYNFM-NSHDSACASA-N

InChI=1S/C15H16O5/c1-17-12-7-11(20-15(16)8-12)4-2-10-3-5-13-14(6-10)19-9-18-13/h3,5-6,8,11H,2,4,7,9H2,1H3/t11-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2401103 | https://www.ncbi.nlm.nih.gov/pubmed/26191127 | https://www.ncbi.nlm.nih.gov/pubmed/26744252 | https://www.ncbi.nlm.nih.gov/pubmed/12383029

Dihydromethysticin is one of the six major kavalactones found in the roots of kava plant. Dihydromethysticin was found to be very effective in producing analgesia in the tail immersion test. Dihydromethysticin kavalactone induces apoptosis in osteosarcoma cells through modulation of PI3K/Akt pathway, disruption of mitochondrial membrane potential and inducing cell cycle arrest. Dihydromethysticin was identified as a promising lung cancer chemopreventive agent. Low concentrations of the kavalactone (+)-dihydromethysticin enhanced the binding of ligands to the GABAA receptors on freeze-dried rat cortex preparations.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Apoptosis 156 Target ID: WP254 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26191127	Activator 1447
Cytochrome P450 3A4 127 Target ID: CHEMBL340 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12127912	Inhibitor 8504	2.5 µM [IC50]
Cytochrome P450 2C19 51 Target ID: CHEMBL3622 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12127912	Inhibitor 8504	0.43 µM [IC50]
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12127912	Inhibitor 8504	13.35 µM [IC50]
Cytochrome P450 1A2 73 Target ID: CHEMBL3356 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12127912	Inhibitor 8504	14.8 µM [IC50]
Cytochrome P450 2D6 62 Target ID: CHEMBL289 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12127912	Inhibitor 8504	37.03 µM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Lung cancer 70 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26744252 https://www.ncbi.nlm.nih.gov/pubmed/27728767 https://www.ncbi.nlm.nih.gov/pubmed/28806079	Preventing	Preclinical	Unknown Approved Use Unknown
Osteosarcoma 22 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26191127	Primary	Basic research	Unknown Approved Use Unknown
Pain 619 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2401103	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Pilot in Vivo Structure-Activity Relationship of Dihydromethysticin in Blocking 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced O6-Methylguanine and Lung Tumor in A/J Mice.	2017-09-28	28806079
Dietary Dihydromethysticin Increases Glucuronidation of 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanol in A/J Mice, Potentially Enhancing Its Detoxification.	2016-03	26744252
Dihydromethysticin kavalactone induces apoptosis in osteosarcoma cells through modulation of PI3K/Akt pathway, disruption of mitochondrial membrane potential and inducing cell cycle arrest.	2015	26191127
Methysticin and 7,8-dihydromethysticin are two major kavalactones in kava extract to induce CYP1A1.	2011-12	21908763
Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro.	2005-10	16033948
Effects of herbal components on cDNA-expressed cytochrome P450 enzyme catalytic activity.	2002-08-16	12127912
Therapeutic potential of kava in the treatment of anxiety disorders.	2002	12383029
Effects of kawain and dihydromethysticin on field potential changes in the hippocampus.	1997-05	9194150
The antinociceptive actions of kava components in mice.	1990-07	2401103

Patents

Sample Use Guides

In Vivo Use Guide

Rat: 1 mg/g of diet

Route of Administration: Oral

In Vitro Use Guide

Dihydromethysticin induced dose-dependent as well as time-dependent antiproliferative effects against MG-63 cell growth. Cell death and apoptotic body formation was noticed followed dihydromethysticin treatment at various doses. The percentage of apoptotic cells (early apoptosis+late apoptosis) increased from 6.63% in untreated control to 23.92%, 23.81% and 93.9% in 25uM, 75uM and 100uM dihydromethysticin-treated cells respectively.

Name

Type

Language

NSC-112159

Preferred Name

English

DIHYDROMETHYSTICIN

Common Name

English

(2S)-2-(2-(1,3-BENZODIOXOL-5-YL)ETHYL)-4-METHOXY-2,3-DIHYDROPYRAN-6-ONE

Systematic Name

English

Classification Tree Code System Code

DSLD

2592 (Number of products:13)