Buparvaquone

Names

[ Name ]:
Buparvaquone

[Synonym ]:
2-[(4-tert-butylcyclohexyl)methyl]-3-hydroxynaphthalene-1,4-dione
2-[[4-(1,1-Dimethylethyl)cyclohexyl]methyl]-3-hydroxy-1,4-naphthalenedione
Butalex
UNII-0354RT7LG4
1,4-Naphthalenedione, 2-[[4-(1,1-dimethylethyl)cyclohexyl]methyl]-3-hydroxy-
2-[(4-tert-Butylcyclohexyl)methyl]-3-hydroxynaphthalen-1,4-dion
2-((4-tert-Butylcyclohexyl)methyl)-3-hydroxy-1,4-naphthochinon
BW 720C
Buparvaquone
Buparvaquonum [Latin]
Buparvacuona [Spanish]
3-(4-t-Butylcyclohexyl)methyl-2-hydroxy-1,4-naphthoquinone
MFCD01712789
2-((4-(1,1-Dimethylethyl)cyclohexyl)methyl)-3-hydroxy-1,4-naphthalenedione
2-[(4-tert-Butylcyclohexyl)methyl]-3-hydroxy-1,4-naphthoquinone
2-Hydroxy-3-{[4-(2-methyl-2-propanyl)cyclohexyl]methyl}-1,4-naphthoquinone
2-((4-tert-Butylcyclohexyl)methyl)-3-hydroxy-1,4-naphthoquinone
1,4-Naphthalenedione, 2-((4-(1,1-dimethylethyl)cyclohexyl)methyl)-3-hydroxy-

Biological Activity

[Description]:

Buparvaquone is a hydroxynaphthoquinone antiprotozoal drug related to parvaquone and atovaquone.

[Related Catalog]:

Signaling Pathways >> Anti-infection >> Parasite

Research Areas >> Infection

[In Vitro]

In 4-day proliferation assays, buparvaquone efficiently inhibits N. caninum tachyzoite replication(IC50=4.9 nM; IC100=100 nM)[1]. Buparvaquone is significantly selective against L. (L.) infantum chagasi intracellular amastigotes, with an IC50 value of 1.5 μM. Other cutaneous species are also susceptible to buparvaquone, with IC50 values in the range 1-4 μM[2].

[In Vivo]

Treatment of N. caninum infected mice with buparvaquone (100 mg/kg) either by intraperitoneal injection or gavage prevents neosporosis symptoms in 4 out of 6 mice in the intraperitoneally treated group, and in 6 out of 7 mice in the group receiving oral treatment[1]. Both a hydrous gel and water-in-oil emulsion of buparvaquone significantly reduce cutaneous parasite burden and lesion size, compared with the untreated control[3].

[Cell Assay]

To study whether pretreatment of host cells prior to invasion had any effect on parasite proliferation, confluent HFF grown in 6-well plates are treated with 1 µM buparvaquone in medium for 1 h or 5 h, and controls are exposed to the corresponding amounts of DMSO. Subsequently, the drug-containing medium is removed and monolayers are ished 4 times with Hank's Balanced Salt Solution, and are infected with Nc-Liv tachyzoites in 5 mL medium without any drug or solvent. After 2 days, cells are collected with a cell scraper, centrifuged, ished once more in PBS, and the pellet is stored at −20 °C prior to quantification of N. caninum proliferation by N. caninum-specific real time PCR as outlined below[1].

[Animal admin]

Mice: On day 0, all mice are infected by intraperitoneal (i.p.) injection of freshly purified N. caninum tachyzoites. After 48 h, mice receive BPQ (100 mg/kg) as suspension in corn oil either by i.p. injection of a volume of 100 µl or by oral application of 100 µl by gavage. The control groups obtained the corresponding amount of the solvent only, either i.p. or orally (see Table 2). The treatments are performed 5 times on a daily basis. If not indicated otherwise, mice are inspected twice daily for clinical signs (ruffled coat, apathy, hind limb paralysis) until day 21 post infection (p.i.), at which time they are euthanized[1].

[References]

[1]. Müller J, et al. Buparvaquone is active against Neospora caninum in vitro and in experimentally infected mice. Int J Parasitol Drugs Drug Resist. 2015 Feb 13;5(1):16-25.

[2]. Reimão JQ, et al. Effectiveness of liposomal buparvaquone in an experimental hamster model of Leishmania (L.) infantum chagasi. Exp Parasitol. 2012 Mar;130(3):195-9.

[3]. Garnier T, et al. In vivo studies on the antileishmanial activity of buparvaquone and its prodrugs. J Antimicrob Chemother. 2007 Oct;60(4):802-10.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
460.7±45.0 °C at 760 mmHg

[ Melting Point ]:
178-184ºC

[ Molecular Formula ]:
C₂₁H₂₆O₃

[ Molecular Weight ]:
326.429

[ Flash Point ]:
246.5±25.2 °C

[ Exact Mass ]:
326.188202

[ PSA ]:
54.37000

[ LogP ]:
6.45

[ Vapour Pressure ]:
0.0±1.2 mmHg at 25°C

[ Index of Refraction ]:
1.574

[ Storage condition ]:
Refrigerator

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QJ5766600

CHEMICAL NAME :: 1,4-Naphthalenedione, 2-((4-(1,1-dimethylethyl)cyclohexyl)methyl)-3-hydroxy -

CAS REGISTRY NUMBER :: 88426-33-9

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C21-H26-O3

MOLECULAR WEIGHT :: 326.47

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: PARAAE Parasitology. (Cambridge University Press, The Edinburgh Bldg., Shaftesbury Rd., Cambridge, CB2 2RU, United Kingdom) V.1- 1908- Volume(issue)/page/year: 90,45,1985

Safety Information

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
QJ5766600

Articles

Drug delivery systems for the topical treatment of cutaneous leishmaniasis.

Expert Opin. Drug Deliv. 9(9) , 1083-97, (2012)

The parenteral administration of pentavalent antimonials for the treatment of all forms of leishmaniasis, including cutaneous leishamniasis (CL), has several limitations. Therapy is long, requiring re...

In-vivo therapeutic efficacy trial with artemisinin derivative, buparvaquone and imidocarb dipropionate against Babesia equi infection in donkeys.

J. Vet. Med. Sci. 65(11) , 1171-7, (2003)

The therapeutic efficacy of imidocarb, artesunate, arteether, buparvaquone and arteether+buparvaquone combination was evaluated against Babesia equi of Indian origin in splenectomised donkeys with exp...

Design, synthesis and in vitro evaluation of novel water-soluble prodrugs of buparvaquone.

Eur. J. Pharm. Sci. 23(2) , 151-8, (2004)

Novel water-soluble phosphate prodrugs (2b-5b) of buparvaquone-oxime (1a) and buparvaquone-O-methyloxime (1b) were synthesized and evaluated in vitro as potential oral prodrugs against leishmaniasis. ...