Betulinic acid

Names

[ CAS No. ]:
472-15-1

[ Name ]:
Betulinic acid

[Synonym ]:
(3β)-3-Hydroxylup-20(29)-en-28-oic acid
Gratiolone
(1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-Hydroxy-1-isopropenyl-5a,5b,8,8,11a-pentamethylicosahydro-3aH-cyclopenta[a]chrysene-3a-carboxylic acid
betulic acid
Platanol
3β-Hydroxy-20(29)-lupaene-28-oic Acid
(3b)-3-hydroxylup-20(29)-en-28-oic Acid
Lup-20(29)-en-28-oic acid, 3β-hydroxy-
Betulinic acid
MFCD00009619
MAIRIN
Lup-20(29)-en-28-oic acid, 3-hydroxy-, (3β)-
Melaleucin
ALS-357
EINECS 207-448-8
Betulinic

Biological Activity

[Description]:

Betulinic acid is a natural pentacyclic triterpenoid, acts as a eukaryotic topoisomerase I inhibitor, with an IC50 of 5 μM, and possesses anti-HIV, anti-malarial, anti-inflammatory and anti-tumor properties.

[Related Catalog]:

Signaling Pathways >> Apoptosis >> Apoptosis

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Anti-infection >> HIV

Signaling Pathways >> Autophagy >> Mitophagy

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

Natural Products >> Terpenoids and Glycosides

Research Areas >> Cancer

Research Areas >> Inflammation/Immunology

Research Areas >> Infection

[Target]

Topoisomerase I:5 μM (IC50)

HIV-1:1.4 μM (EC50)

[In Vitro]

Betulinic acid is a eukaryotic topoisomerase I inhibitor, with an IC50 of 5 μM, and prevents topoisomerase I-DNA interaction[1]. Betulinic acid (10, 20, 40, 80, and 160 µM) significantly suppresses MDA-MB-231 cell viability in a time- and dose-dependent manner after treatment for 24 or 48 h. Betulinic acid (20, 40 µM) causes decrease in Bcl-2 expression of MDA-MB-231 cells. Betulinic acid also induces morphological changes of MDA-MB-231 cells at 20 µM, and leads to ultrastructure changes of MDA-MB-231 cells at 40 µM[2]. Betulinic acid shows anti-HIV activities, with an EC50 of 1.4 µM in acutely infected H9 lymphocytes[4].

[In Vivo]

Betulinic acid (10 and 30 mg/kg, p.o.) significantly abrogates colon shortening, and reduces malondialdehyde (MDA) and lipid hydroperoxide levels in dextran sulfate sodium (DSS)-induced colitis in mice. Betulinic acid (30 mg/kg, p.o.) restores superoxide dismutase (SOD), catalase activity and glutathione (GSH) content to control levels in DSS-induced colitis in mice. Betulinic acid (30 mg/kg, p.o.) also inhibits the DSS-induced increase in inflammatory markers. Betulinic acid (3, 10, 30 mg/kg, p.o.) suppresses acetic acid-induced writhing responses and mustard oil (MO)-induced visceral nociception in mice[3].

[Cell Assay]

CCK-8 is used in the assay. MDA-MB-231 cells are cultured in 96-well plates at a density of 2 × 103 cells/well and then treated with DMSO vehicle or various concentrations of Betulinic acid ranging from 5 µM to 160 µM in 100 µL of medium for the indicated times. After the treatment period, the medium in each well is replaced with 110 µL of medium containing 10 µL of the CCK-8 mixture, and the plates are incubated for 1 h and 30 min at 37°C. The absorbance at a wavelength of 450 nm is measured with a microplate reader[2].

[Animal admin]

Female Swiss albino mice are administered vehicle (5% v/v DMSO in peanut oil) or Betulinic acid (3, 10 or 30 mg/kg) in vehicle, orally. After 1 h, acetic acid (300 mg/kg) is administered by intraperitoneal route and number of writhing response of each animal is counted for 20 min by an observer who is blind to the treatments. Writhing response is when animal rubs its abdomen on surface of table/floor with elongation of the body and extension of the hind limbs[3].

[References]

[1]. Chowdhury AR, et al. Betulinic acid, a potent inhibitor of eukaryotic topoisomerase I: identification of the inhibitory step, the major functional group responsible and development of more potent derivatives. Med Sci Monit. 2002 Jul;8(7):BR254-65.

[2]. Gao Y, et al. Betulinic acid induces apoptosis and ultrastructural changes in MDA-MB-231 breast cancer cells. Ultrastruct Pathol. 2018 Jan-Feb;42(1):49-54.

[3]. Kalra J, et al. Betulinic acid alleviates dextran sulfate sodium-induced colitis and visceral pain in mice. Naunyn Schmiedebergs Arch Pharmacol. 2017 Dec 26.

[4]. Hashimoto F, et al. Anti-AIDS agents--XXVII. Synthesis and anti-HIV activity of betulinic acid and dihydrobetulinic acid derivatives. Bioorg Med Chem. 1997 Dec;5(12):2133-43.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
550.0±33.0 °C at 760 mmHg

[ Melting Point ]:
295-298 °C (dec.)(lit.)

[ Molecular Formula ]:
C₃₀H₄₈O₃

[ Molecular Weight ]:
456.700

[ Flash Point ]:
300.5±21.9 °C

[ Exact Mass ]:
456.360352

[ PSA ]:
57.53000

[ LogP ]:
8.94

[ Vapour Pressure ]:
0.0±3.4 mmHg at 25°C

[ Index of Refraction ]:
1.533

[ Storage condition ]:
Store at +4°C

MSDS

Click to get detail MSDS

Safety Information

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

[ Hazard Codes ]:
Xi

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
3

[ HS Code ]:
2942000000

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2918199090

[ Summary ]:
2918199090 other carboxylic acids with alcohol function but without other oxygen function, their anhydrides, halides, peroxides, peroxyacids and their derivatives。Supervision conditions:None。VAT:17.0%。Tax rebate rate:9.0%。MFN tariff:6.5%。General tariff:30.0%

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