BOLDINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H21NO4
Molecular Weight	327.3743
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]12CC3=CC(O)=C(OC)C=C3C4=C1C(CCN2C)=CC(O)=C4OC

InChI

InChIKey=LZJRNLRASBVRRX-ZDUSSCGKSA-N

InChI=1S/C19H21NO4/c1-20-5-4-10-7-15(22)19(24-3)18-12-9-16(23-2)14(21)8-11(12)6-13(20)17(10)18/h7-9,13,21-22H,4-6H2,1-3H3/t13-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29157166 | https://www.ncbi.nlm.nih.gov/pubmed/29136766 | https://www.ncbi.nlm.nih.gov/pubmed/28826044 | https://www.ncbi.nlm.nih.gov/pubmed/25746354 | https://www.ncbi.nlm.nih.gov/pubmed/28719960

Boldine, an aporphine alkaloid, found abundantly in the leaves/bark of boldo (Peumus boldus Molina) widely consumed in the folk medicine of some regions. Boldine possesses various pharmacological properties including, anticancer activity. It exhibits a significant improvement of learning and memory through inhibition of brain acetylcholinesterase activity and alleviation of brain oxidative stress, which was shown on animal models. Boldine is a potentially useful agent for the treatment of leishmaniosis. In addition, it suppresses osteoclastogenesis, improves bone destruction and may be a potential therapeutic agent for rheumatoid arthritis. Besides, was shown, that boldine inhibits telomerase in cells treated with sub-cytotoxic concentrations. Telomerase inhibition occurs via down-regulation of human telomerase reverse transcriptase (hTERT), the catalytic subunit of the enzyme.

CNS Activity

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Acetylcholinesterase 207 Target ID: P22303\|\|\|Q53F46 Gene ID: 43.0 Gene Symbol: ACHE Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/29136766	Inhibitor 8297
Telomerase reverse transcriptase 10 Target ID: O14746 Gene ID: 7015.0 Gene Symbol: TERT Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25746354	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Leishmaniasis 20 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28719960	Primary	Basic research	Unknown Approved Use Unknown
Rheumatoid arthritis 316 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28826044	Primary	Preclinical	Unknown Approved Use Unknown
Mammary carcinoma 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27611982	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Screening for new compounds with antiherpes activity.	1984 Oct	6517562
Evaluation of natural products as inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase.	1991 Jan-Feb	1710653
Antipoliovirus structure-activity relationships of some aporphine alkaloids.	1998 Apr	9584402
Release of intermediate reactive hydrogen peroxide by macrophage cells activated by natural products.	2001 Feb	11217094
Chemoprotective activity of boldine: modulation of drug-metabolizing enzymes.	2001 Mar	11265593
Effects of some antioxidative aporphine derivatives on striatal dopaminergic transmission and on MPTP-induced striatal dopamine depletion in B6CBA mice.	2003 Feb	12594006
A novel alkaloid antioxidant, Boldine and synthetic antioxidant, reduced form of RU486, inhibit the oxidation of LDL in-vitro and atherosclerosis in vivo in LDLR(-/-) mice.	2004 Apr	15064093
Inhibitory action of conventional food-grade natural antioxidants and of natural antioxidants of new development on the thermal-induced oxidation of cholesterol.	2004 Mar	14985188
Alkaloids from Cassytha filiformis and related aporphines: antitrypanosomal activity, cytotoxicity, and interaction with DNA and topoisomerases.	2004 May	15124084
Protective role of Scoparia dulcis plant extract on brain antioxidant status and lipidperoxidation in STZ diabetic male Wistar rats.	2004 Nov 2	15522116
Photostability and photoprotection factor of boldine and glaucine.	2005 Jul 1	15963438
Structure-affinity relationships of halogenated predicentrine and glaucine derivatives at D1 and D2 dopaminergic receptors: halogenation and D1 receptor selectivity.	2005 Jun 1	15862999
[Alkaloids from the root of Lindera angustifolia].	2005 Oct	16408812
8-NH2-boldine, an antagonist of alpha1A and alpha1B adrenoceptors without affinity for the alpha1D subtype: structural requirements for aporphines at alpha1-adrenoceptor subtypes.	2005 Oct	16254819
Effect of boldine, secoboldine, and boldine methine on angiotensin II-induced neutrophil recruitment in vivo.	2005 Sep	15944212
Boldine and its antioxidant or health-promoting properties.	2006 Jan 5	16221469
Antinociceptive and free radical scavenging activities of alkaloids isolated from Lindera angustifolia Chen.	2006 Jul 19	16513307
Sensitive quantification of apomorphine in human plasma using a LC-ESI-MS-MS method.	2006 Jun	16778727
Are extraction methods in quantitative assays of pharmacopoeia monographs exhaustive? A comparison with pressurized liquid extraction.	2006 Oct	16924586
Antihyperglycemic effect of aporphines and their derivatives in normal and diabetic rats.	2006 Oct	16924583
Advances in development of dopaminergic aporphinoids.	2007 Jan 25	17228858
Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers.	2007 May 15	17391965
Antioxidant and pro-oxidant properties of boldine on hippocampal slices exposed to oxygen-glucose deprivation in vitro.	2008 Nov	18590764
Simultaneous determination of four alkaloids in Lindera aggregata by ultra-high-pressure liquid chromatography-tandem mass spectrometry.	2008 Nov 28	18951552
Boldine: a potential new antiproliferative drug against glioma cell lines.	2009 Dec	19050827
Effect of boldo (Peumus boldus Molina) infusion on lipoperoxidation induced by cisplatin in mice liver.	2009 Jul	19145575
[Simultaneous determination of four alkaloids in Lindera aggregate by high performance liquid chromatography].	2009 Mar	19526789
5-Hydroxytryptamine2A receptor binding activity of compounds from Litsea sessilis.	2009 Mar	18844258
Grandine A, a new proaporphine alkaloid from the bark of Phoebe grandis.	2009 Mar 23	19325519
Ascorbic acid and tetrahydrobiopterin potentiate the EDHF phenomenon by generating hydrogen peroxide.	2009 Nov 1	19592567
The aporphine alkaloid boldine induces adiponectin expression and regulation in 3T3-L1 cells.	2009 Oct	19857072
Cytotoxic thiocarbamate derivatives of boldine.	2010 Oct	21121254
Current and developing therapeutic agents in the treatment of Chagas disease.	2010 Sep 24	20957215
Boldine enhances bile production in rats via osmotic and farnesoid X receptor dependent mechanisms.	2015 May 15	25771127

Sample Use Guides

In Vivo Use Guide

in mice: boldine (1.5, 3 and 6mg/kg, po) for 7 successive days exhibited significant improvement of learning and memory of young and aged mice anticonvulsant effects in mice: boldine (once in a day for 8 days, ip.) in mice: repeated i. p. injections of 30, 60, or 90 mg boldine/kg slowed tumor growth

Route of Administration: Other

In Vitro Use Guide

It was shown that boldine is a potentially useful agent for the treatment of leishmaniasis. The in vitro system consisted of murine macrophage infection with amastigotes of L. amazonensis treated with different concentrations from 50 to 600 μg/ml of boldine for 24 hr. Intracellular parasite destruction was assessed by morphological examination and boldine cytotoxicity to macrophages was tested by the MTT viability assay. When cells were treated with 100 μg/ml of boldine the reduction of parasite infection was 81% compared with untreated cultures cells.

Name

Type

Language

BOLDINE

Common Name

English

(6AS)-5,6,6A,7-TETRAHYDRO-1,10-DIMETHOXY-6-METHYL-4H-DIBENZO(DE,G)QUINOLINE-2,9-DIOL

Common Name

English

BOLDINE [MI]

Common Name

English

1,10-DIMETHOXY-2,9-DIHYDROXYAPORPHINE

Systematic Name

English

Boldine [WHO-DD]

Common Name

English

1,10-DIMETHOXY-6A.ALPHA.-APORPHINE-2,9-DIOL

Common Name

English

(S)-BOLDINE

Common Name

English

2,6-DIHYDROXY-3,5-DIMETHOXYAPORPHINE

Common Name

English

NSC-65689

Code

English

BOLDINE [EP MONOGRAPH]

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/13/1226