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=C(C=CC=C3)C2=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 8504
nitric oxide biosynthetic process 17 Target ID: GO:0006809 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9644055	Activator 1447
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 846

Conditions

Condition	Modality	Targets	Highest Phase	Product
Malaria 96 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
Synthesis and antimalarial evaluation of some 4-quinazolinone derivatives based on febrifugine.	2010-10	22247880
Synthesis and evaluation of 4-quinazolinone compounds as potential antimalarial agents.	2010-09	20538379
Dihydroxylation of vinyl sulfones: stereoselective synthesis of (+)- and (-)-febrifugine and halofuginone.	2010-01-15	20000346
A new reaction motif: "homo-S(N)2'-like" direct nucleophilic addition to neutral eta(3)-allylmolybdenum complexes. total synthesis of the antimalarial (+)-isofebrifugine.	2009-09-09	19678704
Effects of limonoids from Cipadessa fruticosa on fall armyworm.	2009-08-15	19678552
Complementary chemoenzymatic routes to both enantiomers of febrifugine.	2009-07-21	19582308
Synthesis and biological evaluation of febrifugine analogues as potential antimalarial agents.	2009-07-01	19467876
Synthesis and comparison of antimalarial activity of febrifugine derivatives including halofuginone.	2009-05	19442220
Halofuginone prevents extracellular matrix deposition in diabetic nephropathy.	2009-02-06	19114027
Possible involvement of IFN-gamma in early mortality of Plasmodium berghei NK65-infected BALB/c mice after febrifugine treatment.	2008-11	19062681
Asymmetric synthesis of (+)-isofebrifugine and (-)-sedacryptine from a common chiral nonracemic building block.	2008-09-04	18672881
Differentiation of the diastereomeric synthetic precursors of isofebrifugine and febrifugine by electrospray ionization tandem mass spectrometry.	2008-07	18561280
Recent advances in antimalarial compounds and their patents.	2007	17346161
Febrifugine derivative antimalarial activity: quantum mechanical predictors.	2006-11-16	18327483
Exploration of a new type of antimalarial compounds based on febrifugine.	2006-07-27	16854076
Synthesis and evaluation of febrifugine analogues as potential antimalarial agents.	2006-04-01	16434194
Antimalarials: shortages and searches.	2005-10	16249521
Concise synthesis of dl-febrifugine.	2005-07	15997158
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.	2004-10	15338283
Combination effects of chloroquine with the febrifugine and isofebrifugine mixture against a blood-induced infection with chloroquine-resistant Plasmodium berghei NK65 in ICR mice.	2003-12	14669265
Metabolites of febrifugine and its synthetic analogue by mouse liver S9 and their antimalarial activity against Plasmodium malaria parasite.	2003-09-25	13678413
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.	2003-06	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.	2003-06	12820231
Re-revision of the stereo structure of piperidine lactone, an intermediate in the synthesis of febrifugine.	2002-07	12130869
Potent antimalarial febrifugine analogues against the plasmodium malaria parasite.	2002-06-06	12036365
Lewis acid-catalyzed ring-opening reactions of semicyclic N,O-acetals possessing an exocyclic nitrogen atom: mechanistic aspect and application to piperidine alkaloid synthesis.	2001-12-19	11741414
Synthesis and antimalarial activity of febrifugine derivatives.	2001-06	11411524
A concise enantioselective synthesis of antimalarial febrifugine alkaloids.	2001-03-22	11263924
Efficient synthesis of piperidine derivatives. Development of metal triflate-catalyzed diastereoselective nucleophilic substitution reactions of 2-methoxy- and 2-acyloxypiperidines.	2001-02-09	11430100

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 `Mon Mar 31 19:08:05 GMT 2025` Edited by `admin` on `Mon Mar 31 19:08:05 GMT 2025`
Record UNII	89UWD0FH2I
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DICHROIN B

Preferred Name

English

FEBRIFUGINE

Common Name

English

NSC-315535

Code

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