Beta-Lapachone

Names

[ Name ]:
Beta-Lapachone

[Synonym ]:
2H-Naphtho[1,2-b]pyran-5,6-dione, 3,4-dihydro-2,2-dimethyl-
3,4-Dihydro-2,2-dimethyl-2H-naphtho(1,2-b)pyran-5,6-dione
Beta-Lapachone
3,4-Dihydro-2,2-dimethyl-2H-naphtho[2,3-b]pyran-5,10-dione
β-lapachone
3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]-pyran-5,6-dione
2,2-Dimethyl-3,4-dihydro-2H-benzo[h]chromene-5,6-dione
2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione
ARQ-501
CO-501

Biological Activity

[Description]:

β-Lapachone is a naturally occurring O-naphthoquinone, acts as a topoisomerase I inhibitor, and induces apoptosis by inhibiting cell cycle progression.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Cell Cycle/DNA Damage >> Topoisomerase

Research Areas >> Cancer

Natural Products >> Quinones

[Target]

Topoisomerase I

[In Vitro]

β-Lapachone is a topoisomerase I inhibitor. β-Lapachone (25 μM) inhibits camptothecin-induced DNA cleavage[1]. β-Lapachone (10-40 μM) significantly reduces the colony-forming ability of CHO cells, and is cytotoxic in S phase. β-Lapachone at above 10 μM, causes a heavy DNA-strand breaks in CHO cells[2]. β-Lapachone (10 μM) suppresses JCPyV replication in IMR-32 cells. β-Lapachone (1.0 µM) potently affects JCPyV propagation in JCI cells. β-Lapachone (0.01-0.1 μM) inhibits VP1 production in JCI cells[4].

[In Vivo]

β-Lapachone (0.066%) ameliorates cisplatin-induced renal injury and when in combination with cisplatin, the affect is more significant in mice. β-Lapachone increases Mre11-Rad50-Nbs1 (MRN) complex expression in mice[3].

[Kinase Assay]

DNA topoisomerase I is incubated in the presence or absence of drugs (including β-Lapachone), in 20 μL of relaxation buffer (50 mM Tris (pH 7.5). 50 mM KCl, 10 mM MgCl2, 0.5 mM dithiothreitol, 0.5 mM EDTA, 30 μg/mL bovine serum albumin) for 30 min at 37°C. Reactions are stopped by adding 1% SDS and proteinase K (50 μg/mL). After an additional 1-h incubation at 37°C, the products are separated by electrophoresis in 1% agarose gel in TAE buffer (0.04 M tris acetate, 0.001 M EDTA). The gel is stained with ethidium bromide after electrophoresis. The photographic negative is scanned with an NIH image analysis system[1].

[Cell Assay]

Cytotoxicity is measured by an MTT assay. IMR-32 and JCI cells are plated in 96-well microtiter plates at a concentration of 5.0 × 104 (topotecan) or 2.5 × 104 (β-lapachone) cells/well/100 µL medium 24 hr prior to addition of various concentrations of topotecan or β-lapachone. The cells are then incubated for 72 hr at 37°C in a CO2 incubator. Cell proliferation is assessed using a Cell Proliferation Kit I. Experiments are performed using four independent cultures[4].

[Animal admin]

Male Balb/c mice are provided a commercial pellet diet and water ad libitum. After 1 week of acclimation, the mice are randomly allocated to one of the following groups (5 per group): control, β-lapachone, cisplatin (18 mg/kg, ip), and β-lapachone + cisplatin (18 mg/kg, ip). The β-lapachone groups are fed a diet containing the drug (0.066) for 2 weeks prior to cisplatin injection. All mice are sacrificed under carbon dioxide anesthesia 3 days after cisplatin injection. The blood samples are subjected to serum BUN and CRE analyses. Half of the kidney is quickly removed for histopathological and immunohistochemical (IHC) studies. The other half is stored at −70°C until western blot assay[3].

[References]

[1]. Li CJ, et al. beta-Lapachone, a novel DNA topoisomerase I inhibitor with a mode of action different from camptothecin. J Biol Chem. 1993 Oct 25;268(30):22463-8.

[2]. Vanni A, et al. DNA damage and cytotoxicity induced by beta-lapachone: relation to poly(ADP-ribose) polymerase inhibition. Mutat Res. 1998 Jun 5;401(1-2):55-63.

[3]. Kim TW, et al. β-Lapachone enhances Mre11-Rad50-Nbs1 complex expression in cisplatin-induced nephrotoxicity. Pharmacol Rep. 2016 Feb;68(1):27-31.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
381.4±42.0 °C at 760 mmHg

[ Melting Point ]:
>110ºC (dec.)

[ Molecular Formula ]:
C₁₅H₁₄O₃

[ Molecular Weight ]:
242.270

[ Flash Point ]:
169.7±27.9 °C

[ Exact Mass ]:
242.094299

[ PSA ]:
43.37000

[ LogP ]:
2.82

[ Vapour Pressure ]:
0.0±0.9 mmHg at 25°C

[ Index of Refraction ]:
1.595

[ Storage condition ]:
-20?C Freezer

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QL6127400

CHEMICAL NAME :: 2H-Naphtho(1,2-b)pyran-5,6-dione, 3,4-dihydro-2,2-dimethyl-

CAS REGISTRY NUMBER :: 4707-32-8

BEILSTEIN REFERENCE NO. :: 0181499

LAST UPDATED :: 199612

DATA ITEMS CITED :: 2

MOLECULAR FORMULA :: C15-H14-O3

MOLECULAR WEIGHT :: 242.29

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

MUTATION DATA

TYPE OF TEST :: Sister chromatid exchange

TEST SYSTEM :: Rodent - hamster Ovary

DOSE/DURATION :: 1 umol/L

REFERENCE :: MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 288,263,1993

Safety Information

[ Personal Protective Equipment ]:
Eyeshields;Gloves;type N95 (US);type P1 (EN143) respirator filter

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ RTECS ]:
QL6127400

[ HS Code ]:
2914399090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2914399090

[ Summary ]:
2914399090. other aromatic ketones without other oxygen function. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:5.5%. General tariff:30.0%

Articles

Light effect on the stability of β-lapachone in solution: pathways and kinetics of degradation.

J. Pharm. Pharmacol. 63(9) , 1156-60, (2011)

The purpose of this work was to study the chemical stability of the new antitumoral β-lapachone (βLAP) to determine the degradation pathway/s of the molecule and the degradation kinetics in addition t...

Temperature-sensitive gels for intratumoral delivery of β-lapachone: effect of cyclodextrins and ethanol.

ScientificWorldJournal 2012 , 126723, (2012)

This work evaluated the potential of Pluronics (varieties F127 and P123) in combination with solubilizing agents to be used as syringeable in situ gelling depots of intratumoral β-lapachone (βLAP). Pl...

Ultrastructural analysis of β-lapachone-induced surface membrane damage in male adult Schistosoma mansoni BH strain worms.

Exp. Parasitol. 142 , 83-90, (2014)

The present study provides, for the first time, conclusions on the in vitro schistosomicidal properties of β-lap. Adult male Schistosoma mansoni worms of the BH strain were used for the study. Motilit...