Aloperine is an alkaloid found in the roots of S. flavescenswith with diverse biological activities including antiviral, anticancer, antioxidant, and anti-inflammatory actions. At concentrations well below the cytotoxic concentration (CC50) of >86.5 μM in vitro, it prevents HIV-1 replication and envelope-mediated cell-cell fusion (EC50s = 1.75 and 1.2 μM, respectively). With IC50 values of 40, 270, and 360 M, respectively, aloperine inhibits the growth of the leukemia cell lines HL-60, U937, and K562. In a rat model of pulmonary hypertension, administration of aloperine at a dose of 60 mg/kg decreases the expression of NOX2, NOX4, superoxide dismutase, and glutathione peroxidase in the lungs.In a mouse model of allergic contact dermatitis, topical application of aloperine decreases ear erythema, swelling, and the production of the inflammatory cytokines TNF-α, IL-1β, and IL-6.
Physicochemical Properties
| Molecular Formula | C15H24N2 |
| Molecular Weight | 232.3645 |
| Exact Mass | 232.193 |
| Elemental Analysis | C, 77.53; H, 10.41; N, 12.06 |
| CAS # | 56293-29-9 |
| Related CAS # | 56293-29-9 |
| PubChem CID | 162147 |
| Appearance | White to off-white solid powder |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 367.7±37.0 °C at 760 mmHg |
| Melting Point | 69 - 71ºC |
| Flash Point | 155.8±17.5 °C |
| Vapour Pressure | 0.0±0.8 mmHg at 25°C |
| Index of Refraction | 1.583 |
| LogP | 3.21 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 2 |
| Rotatable Bond Count | 0 |
| Heavy Atom Count | 17 |
| Complexity | 336 |
| Defined Atom Stereocenter Count | 4 |
| SMILES | N12C([H])([H])C([H])([H])C([H])([H])C([H])([H])[C@]1([H])[C@@]1([H])C([H])=C3C([H])([H])C([H])([H])C([H])([H])N([H])[C@@]3([H])[C@@]([H])(C2([H])[H])C1([H])[H] |
| InChi Key | SKOLRLSBMUGVOY-GBJTYRQASA-N |
| InChi Code | InChI=1S/C15H24N2/c1-2-7-17-10-13-9-12(14(17)5-1)8-11-4-3-6-16-15(11)13/h8,12-16H,1-7,9-10H2/t12-,13+,14+,15+/m0/s1 |
| Chemical Name | (1R,2S,9R,10R)-3,15-diazatetracyclo[7.7.1.02,7.010,15]heptadec-7-ene |
| Synonyms | Aloperine |
| HS Tariff Code | 2934.99.03.00 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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
| ln Vitro | Aloperine treatment exerts the strongest cytotoxic activity against human cancer cell lines of various tissue origins, including leukemia cell lines HL-60, U937, and K562, oesophageal cancer EC109 cells, lung cancer A549 cells, and hepatocellular carcinoma HepG2 cell line, with IC50 values of 0.04 mM, 0.27 mM, 0.36 mM, 1.11 mM, 1.18 mM, and 1. The strongest cytotoxic effect of aloperine on HL-60 cells is seen at 72 hours, with an inhibition rate of 94.1%. Up to 1 mM of aloperine has no discernible impact on the viability of normal PBMNCs at 72 hours, in contrast to how it affects leukaemia cells. Aloperine treatment at 20 μM for 48 hours significantly and dose-dependently induces apoptosis and autophagy in HL-60 cells.[2] |
| ln Vivo | Topical administration of 1% aloperine inhibits 2, 4-dinitrofluorobenzene (DNFB)-induced ear thickness and erythema in BALB/c mice and significantly reduces the up-regulated mRNA and protein levels of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6) induced by DNFB in ear biopsy homogenates. [1] Aloperine, when applied topically, dose-dependently reduces the DNFB-induced dermatitis (dermatitis index and ear thickness) in NC/Nga mice on days 13 and 14. Treatment with aloperine decreases DNFB-induced lymphocyte and eosinophil infiltration in a dose-dependent way. Treatment with aloperine also decreases the dose-dependent infiltration of mast cells brought on by DNFB. In a dose-dependent manner, aloperine lowers the plasma level of IgE. Aloperine increases the level of IL-10 in a dose-dependent manner while markedly decreasing the DNFB-induced increase in IL-4, IL-13, and IFN-γ productions. TNF-α, IL-1β, and IL-6 cytokine levels in NC/Nga mouse ear biopsies are significantly and dose-dependently reduced by aloperine treatment. [3] |
| Cell Assay | Cells are seeded in 96-well plates in 100-μL culture medium. Aloperine or excipient control-containing experimental media are added to the appropriate wells following incubation times of 4 hours for leukemia cells and 24 hours for solid cancer cells. The in vitro IC50 growth inhibitory values of aloperine in cancer cells are calculated after treatment with five concentrations of aloperine for 48 hours. Each well receives 10 μL of MTT solution (5 mg/mL) following incubation. Following that, the plates are incubated for 4 hours at 37 °C. 100 μL of isopropanol-HCI-SDS solution are added to each well to dissolve intracellular formazan crystals. The samples' optical densities are measured at 570 nm following an overnight incubation at 37°C. The analysis of DNA fragmentation is performed using an apoptotic DNA ladder kit after DNA has been extracted from cells that have been exposed to the recommended doses of aloperine for 48 hours. Cells are gathered and incubated in PBS containing 5 μM acridine orange for 15 minutes in order to detect autophagy. In 100 μL of PBS, the cells are resuspended after the acridine orange has been removed. With an inverted fluorescent microscope, fluorescent micrographs can be taken. The average number of cells with intense red staining for three fields, each with at least 50 cells, is used to calculate the amount of autophagy occurring in each experimental condition. |
| Animal Protocol |
Female BALB/c mice with DNFB-induced allergic contact dermatitis 1% (w/w) Topical application |
| References |
[1]. Eur J Pharmacol . 2010 Mar 10;629(1-3):147-52. [2]. Basic Clin Pharmacol Toxicol . 2011 May;108(5):304-9. [3]. Eur J Pharmacol . 2011 May 11;658(2-3):263-9. |
| Additional Infomation | Aloperine has been reported in Sophora jaubertii, Thinicola incana, and other organisms with data available. |
Solubility Data
| Solubility (In Vitro) |
DMSO: 5.6~46 mg/mL (23.9~198.0 mM) Water: ~12 mg/mL (~51.6 mM) Ethanol: ~46 mg/mL (~198.0 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.95 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.95 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (8.95 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.3037 mL | 21.5183 mL | 43.0367 mL | |
| 5 mM | 0.8607 mL | 4.3037 mL | 8.6073 mL | |
| 10 mM | 0.4304 mL | 2.1518 mL | 4.3037 mL |