 Chemical Structure.png)
Betulinic acid (also known as ALS-357; LS-357; Mairin; Lupatic acid; Betulic acid) is a naturally occuring pentacyclic triterpenoid extracted from Syzigium claviflorum that displays anti-HIV and antitumor activity. Through an EC50 of 1.4 μ M, Betulinic acid inhibits HIV-1. By directly triggering the mitochondrial pathway of apoptosis in tumor cells in a way that is independent of both CD95 and p53, Betulinic acid specifically causes apoptosis in these cells. With an EC50 of 1.04 μM, Betulinic acid also exhibits TGR5 agonist activity.
Physicochemical Properties
| Molecular Formula | C30H48O3 | |
| Molecular Weight | 456.7 | |
| Exact Mass | 456.36 | |
| Elemental Analysis | C, 78.90; H, 10.59; O, 10.51 | |
| CAS # | 472-15-1 | |
| Related CAS # |
|
|
| PubChem CID | 64971 | |
| Appearance | White to off-white solid powder | |
| Density | 1.1±0.1 g/cm3 | |
| Boiling Point | 550.0±33.0 °C at 760 mmHg | |
| Melting Point | 295-298 °C (dec.)(lit.) | |
| Flash Point | 300.5±21.9 °C | |
| Vapour Pressure | 0.0±3.4 mmHg at 25°C | |
| Index of Refraction | 1.533 | |
| LogP | 8.94 | |
| Hydrogen Bond Donor Count | 2 | |
| Hydrogen Bond Acceptor Count | 3 | |
| Rotatable Bond Count | 2 | |
| Heavy Atom Count | 33 | |
| Complexity | 861 | |
| Defined Atom Stereocenter Count | 10 | |
| SMILES | O([H])[C@@]1([H])C([H])([H])C([H])([H])[C@@]2(C([H])([H])[H])[C@]([H])(C1(C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])[C@]1(C([H])([H])[H])[C@]2([H])C([H])([H])C([H])([H])[C@]2([H])[C@@]3([H])[C@]([H])(C(=C([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])[C@]3(C(=O)O[H])C([H])([H])C([H])([H])[C@@]12C([H])([H])[H] |
|
| InChi Key | QGJZLNKBHJESQX-FZFNOLFKSA-N | |
| InChi Code | InChI=1S/C30H48O3/c1-18(2)19-10-15-30(25(32)33)17-16-28(6)20(24(19)30)8-9-22-27(5)13-12-23(31)26(3,4)21(27)11-14-29(22,28)7/h19-24,31H,1,8-17H2,2-7H3,(H,32,33)/t19-,20+,21-,22+,23-,24+,27-,28+,29+,30-/m0/s1 | |
| Chemical Name | (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-hydroxy-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylic acid | |
| Synonyms |
|
|
| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
|
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Topoisomerase I ( IC50 = 5 μM ); HIV-1 ( IC50 = 1.4 μM ); NF-κB | |
| ln Vitro |
|
|
| ln Vivo |
|
|
| Enzyme Assay | The 25-mer annealed duplex consisting of oligonucleotide-1 and oligonicleotide-2 is subjected to an 8°C incubation period with 25 or 50 units of rat liver topoisomerase I, either in the presence or absence of betulinic acid in the binding buffer. Following incubation, the reaction mixtures are electrophoresed in a 7% non-denaturing polyacrylamide gel in 0.167 × TBE buffer at 4 °C. Ethidium bromide is then used to stain the DNA bands. | |
| Cell Assay | The assay makes use of CCK-8. After being grown at a density of 2 × 103 cells/well in 96-well plates, MDA-MB-231 cells are treated with DMSO vehicle or different concentrations of betulinic acid (5 µM to 160 µM) in 100 µL of medium for the specified durations. Following the treatment phase, 110 µL of medium containing 10 µL of the CCK-8 mixture is added to each well, and the plates are incubated at 37°C for one hour and thirty minutes. With the aid of a microplate reader, the absorbance at 450 nm wavelength is determined[2]. | |
| Animal Protocol |
|
|
| References |
[1]. 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]. Betulinic acid induces apoptosis and ultrastructural changes in MDA-MB-231 breast cancer cells. Ultrastruct Pathol. 2018 Jan-Feb;42(1):49-54. [3]. Betulinic acid alleviates dextran sulfate sodium-induced colitis and visceral pain in mice. Naunyn Schmiedebergs Arch Pharmacol. 2017 Dec 26. [4]. 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. [5]. Betulinic acid as new activator of NF-kappaB: molecular mechanisms and implications for cancer therapy. Oncogene. 2005 Oct 20;24(46):6945-56. |
|
| Additional Infomation |
Betulinic acid is a pentacyclic triterpenoid that is lupane having a double bond at position 20(29) as well as 3beta-hydroxy and 28-carboxy substituents. It is found in the bark and other plant parts of several species of plants including Syzygium claviflorum. It exhibits anti-HIV, antimalarial, antineoplastic and anti-inflammatory properties. It has a role as an EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor, an anti-HIV agent, an antimalarial, an anti-inflammatory agent, an antineoplastic agent and a plant metabolite. It is a pentacyclic triterpenoid and a hydroxy monocarboxylic acid. It derives from a hydride of a lupane. Betulinic Acid has been used in trials studying the treatment of Dysplastic Nevus Syndrome. Betulinic acid has been reported in Paeonia emodi, Bowdichia virgilioides, and other organisms with data available. Betulinic Acid is a pentacyclic lupane-type triterpene derivative of betulin (isolated from the bark of Betula alba, the common white birch) with antiinflammatory, anti-HIV and antineoplastic activities. Betulinic acid induces apoptosis through induction of changes in mitochondrial membrane potential, production of reactive oxygen species, and opening of mitochondrial permeability transition pores, resulting in the release of mitochondrial apogenic factors, activation of caspases, and DNA fragmentation. Although originally thought to exhibit specific cytotoxicity against melanoma cells, this agent has been found to be cytotoxic against non-melanoma tumor cell types including neuroectodermal and brain tumor cells. A lupane-type triterpene derivative of betulin which was originally isolated from BETULA or birch tree. It has anti-inflammatory, anti-HIV and antineoplastic activities. See also: Paeonia lactiflora root (part of); Jujube fruit (part of). |
Solubility Data
| Solubility (In Vitro) |
DMSO: 20~35.7 mg/mL (43.8~78.2 mM) Ethanol: 10 mg/mL (~21.9 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 4 mg/mL (8.76 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1896 mL | 10.9481 mL | 21.8962 mL | |
| 5 mM | 0.4379 mL | 2.1896 mL | 4.3792 mL | |
| 10 mM | 0.2190 mL | 1.0948 mL | 2.1896 mL |