FEBRIFUGINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C16H19N3O3
Molecular Weight	301.3404
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O[C@H]1CCCN[C@@H]1CC(=O)CN2C=NC3=CC=CC=C3C2=O

InChI

InChIKey=FWVHWDSCPKXMDB-CABCVRRESA-N

InChI=1S/C16H19N3O3/c20-11(8-14-15(21)6-3-7-17-14)9-19-10-18-13-5-2-1-4-12(13)16(19)22/h1-2,4-5,10,14-15,17,21H,3,6-9H2/t14-,15+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C16H19N3O3
Molecular Weight	301.3404
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://wiredspace.wits.ac.za/bitstream/handle/10539/1743/01chapter1.pdf
Curator's Comment: description was created based on several sources, including: Weici Tang, Gerhard Eisenbrand (2013) "Chinese Drugs of Plant Origin", p.455-457 Retrieved from https://books.google.ru/books?id=xmHwCAAAQBAJ

The alkaloids febrifugine was originally isolated from the roots of the Chinese shrub Dichroa febrifuga. Febrifugine showed an antimalarial activity 50-100 times higher than that of quinine. Febrifugine acts by causing an increase in NO production during the immunological response - increased production of NO by febrifugine plays an important role in host defense against malaria infection in mice. Also, febrifugine are known to inhibit prolyl-tRNA synthetase of malaria parasite Plasmodium falciparum.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Proline--tRNA ligase 2 Target ID: Q8I5R7 Gene ID: 811187.0 Gene Symbol: proRS Target Organism: Plasmodium falciparum (isolate 3D7) Sources: https://www.ncbi.nlm.nih.gov/pubmed/22327401 \| https://www.ncbi.nlm.nih.gov/pubmed/25047712 \| https://www.ncbi.nlm.nih.gov/pubmed/25995223	Inhibitor 8297
nitric oxide biosynthetic process 17 Target ID: GO:0006809 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9644055	Activator 1430
Hemozoin formation 2 Target ID: Hemozoin formation Sources: Teng, W.-C. et al. (2016) "Medicinal Plants and Malaria: Applications, Trends, and Prospects", chapter.4.1.3.1 Retrieved from \| https://books.google.ru/books?id=CBXYCwAAQBAJ	Modulator 828

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malaria 95 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10535750 https://www.ncbi.nlm.nih.gov/pubmed/12820231 https://www.ncbi.nlm.nih.gov/pubmed/11009379 https://www.ncbi.nlm.nih.gov/pubmed/9644055	Curative		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Lewis acid-catalyzed ring-opening reactions of semicyclic N,O-acetals possessing an exocyclic nitrogen atom: mechanistic aspect and application to piperidine alkaloid synthesis.	2001 Dec 19	11741414
Efficient synthesis of piperidine derivatives. Development of metal triflate-catalyzed diastereoselective nucleophilic substitution reactions of 2-methoxy- and 2-acyloxypiperidines.	2001 Feb 9	11430100
Synthesis and antimalarial activity of febrifugine derivatives.	2001 Jun	11411524
A concise enantioselective synthesis of antimalarial febrifugine alkaloids.	2001 Mar 22	11263924
Re-revision of the stereo structure of piperidine lactone, an intermediate in the synthesis of febrifugine.	2002 Jul	12130869
Potent antimalarial febrifugine analogues against the plasmodium malaria parasite.	2002 Jun 6	12036365
Combination effects of chloroquine with the febrifugine and isofebrifugine mixture against a blood-induced infection with chloroquine-resistant Plasmodium berghei NK65 in ICR mice.	2003 Dec	14669265
Different responses of three rodent Plasmodia species, Plasmodium yoelii 17XL, P. berghei NK65 and P. chabaudi AS on treatment with febrifugine and isofebrifugine mixture from Hydrangea macrophylla var. Otaksa leaf in ICR mice.	2003 Jun	12820234
Comparison of antimalarial activity of the alkaloidal fraction of Hydrangea macrophylla var. Otaksa leaves with the hot-water extract in ICR mice infected with Plasmodium yoelii 17 XL.	2003 Jun	12820231
Metabolites of febrifugine and its synthetic analogue by mouse liver S9 and their antimalarial activity against Plasmodium malaria parasite.	2003 Sep 25	13678413
Cytokine and antibody production during the course of resolution in Plasmodium yoelii 17XL-infected BALB/c mice treated with febrifugine and isofebrifugine mixture from leaves of Hydrangea macrophylla var. Otaksa.	2004 Oct	15338283
Concise synthesis of dl-febrifugine.	2005 Jul	15997158
Antimalarials: shortages and searches.	2005 Oct	16249521
Synthesis and evaluation of febrifugine analogues as potential antimalarial agents.	2006 Apr 1	16434194
Exploration of a new type of antimalarial compounds based on febrifugine.	2006 Jul 27	16854076
Recent advances in antimalarial compounds and their patents.	2007	17346161
Febrifugine derivative antimalarial activity: quantum mechanical predictors.	2008 Jan-Feb	18327483
Differentiation of the diastereomeric synthetic precursors of isofebrifugine and febrifugine by electrospray ionization tandem mass spectrometry.	2008 Jul	18561280
Possible involvement of IFN-gamma in early mortality of Plasmodium berghei NK65-infected BALB/c mice after febrifugine treatment.	2008 Nov	19062681
Asymmetric synthesis of (+)-isofebrifugine and (-)-sedacryptine from a common chiral nonracemic building block.	2008 Sep 4	18672881
Halofuginone prevents extracellular matrix deposition in diabetic nephropathy.	2009 Feb 6	19114027
Synthesis and biological evaluation of febrifugine analogues as potential antimalarial agents.	2009 Jul 1	19467876
Complementary chemoenzymatic routes to both enantiomers of febrifugine.	2009 Jul 21	19582308
Synthesis and comparison of antimalarial activity of febrifugine derivatives including halofuginone.	2009 May	19442220
Effects of limonoids from Cipadessa fruticosa on fall armyworm.	2009 May-Jun	19678552
A new reaction motif: "homo-S(N)2'-like" direct nucleophilic addition to neutral eta(3)-allylmolybdenum complexes. total synthesis of the antimalarial (+)-isofebrifugine.	2009 Sep 9	19678704
Dihydroxylation of vinyl sulfones: stereoselective synthesis of (+)- and (-)-febrifugine and halofuginone.	2010 Jan 15	20000346
Synthesis and antimalarial evaluation of some 4-quinazolinone derivatives based on febrifugine.	2010 Oct	22247880
Synthesis and evaluation of 4-quinazolinone compounds as potential antimalarial agents.	2010 Sep	20538379

Patents

Sample Use Guides

In Vivo Use Guide

dosage range - 50 ug/kg/day - 5.00 mg/kg/day once daily

Route of Administration: Oral

In Vitro Use Guide

Febrifugine exhibits extreme potency against P. falciparum. Its activity is approximately 10-fold that of the effective antimalarial artemisinin, and 25-fold that of the well-known drug (EC50=0.7 nM). chloroquine.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 18:12:13 UTC 2023` Edited by `admin` on `Fri Dec 15 18:12:13 UTC 2023`
Record UNII	89UWD0FH2I
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

FEBRIFUGINE

Common Name

English

NSC-315535

Code

English

DICHROIN B

Brand Name

English

TRANS-(+)-FEBRIFUGINE

Common Name

English

.BETA.-DICHROIN

Common Name

English

3-(3-((2R,3S)-3-HYDROXY-2-PIPERIDINYL)-2-OXOPROPYL)-4(3H)-QUINAZOLINONE

Systematic Name

English

FEBRIFUGINE [MI]

Common Name

English

.BETA.-DICHROINE

Common Name

English

Code System Code Type Description

FDA UNII

89UWD0FH2I