 Chemical Structure.png)
Cyclovirobuxine D (also known as CVB-D or Bebuxine) is a naturally occurring and bioactive substance that was isolated from the Buxus microphylla and has been used to treat acute myocardial ischemia. The human breast cancer cell line MCF-7 may be induced to undergo autophagy by the alkaloid cyclovirobuxine D, which is found in a traditional Chinese herb. In rats with experimental myocardial injury brought on by sympathetic overactivity, it has a preventing effect against oxidative stress and energy metabolism. Additionally, Cyclovirobuxine D helps treat heart failure brought on by myocardial infarction, which supports its potential as a new treatment for heart failure.
Physicochemical Properties
| Molecular Formula | C26H46N2O | |
| Molecular Weight | 402.66 | |
| Exact Mass | 402.361 | |
| Elemental Analysis | C, 77.55; H, 11.52; N, 6.96; O, 3.97 | |
| CAS # | 860-79-7 | |
| Related CAS # |
|
|
| PubChem CID | 260439 | |
| Appearance | White to off-white solid powder | |
| Density | 1.1±0.1 g/cm3 | |
| Boiling Point | 495.7±10.0 °C at 760 mmHg | |
| Flash Point | 34.1±9.6 °C | |
| Vapour Pressure | 0.0±2.9 mmHg at 25°C | |
| Index of Refraction | 1.551 | |
| LogP | 4.86 | |
| Hydrogen Bond Donor Count | 3 | |
| Hydrogen Bond Acceptor Count | 3 | |
| Rotatable Bond Count | 3 | |
| Heavy Atom Count | 29 | |
| Complexity | 692 | |
| Defined Atom Stereocenter Count | 10 | |
| SMILES | C[C@@]12C[C@@H](O)[C@H]([C@H](C)NC)[C@@]1(C)CC[C@@]13C[C@]41CC[C@H](NC)C(C)(C)[C@@H]4CC[C@@H]23 |
|
| InChi Key | GMNAPBAUIVITMI-ABNIRSKTSA-N | |
| InChi Code | InChI=1S/C26H46N2O/c1-16(27-6)21-17(29)14-24(5)19-9-8-18-22(2,3)20(28-7)10-11-25(18)15-26(19,25)13-12-23(21,24)4/h16-21,27-29H,8-15H2,1-7H3/t16-,17+,18-,19-,20-,21-,23+,24-,25+,26-/m0/s1 | |
| Chemical Name | (1S,3R,6S,8R,11S,12S,14R,15S,16R)-7,7,12,16-tetramethyl-6-(methylamino)-15-[(1S)-1-(methylamino)ethyl]pentacyclo[9.7.0.01,3.03,8.012,16]octadecan-14-ol | |
| 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 |
|
| 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 | Natural alkaloid; autophagy; Akt; mTOR[1] |
| ln Vitro | Only 10% of MGC-803 cells and 20% of MKN28 cells survived 72 hours after treatment with cyclobuxine D (0-240 µM; 24-72 hours) due to a concentration- and time-dependent decrease in cell viability following CVB-D therapy[2]. Gastric cancer cells' cell cycle is stopped in the S phase in a concentration-dependent manner by cyclobuxine D (0-120 µM; 48 hours) [2]. Cyclovirobuxine D (0-120 µM; 48 hours) induces concentration-dependent apoptosis in gastric cancer cells, particularly early apoptosis. In gastric cancer cells, cyclobuxine D (0-120 µM; 48 hours) induces apoptosis via upregulating cleaved Caspase-3, Bax/Bcl-2 ratio, and other apoptosis-related proteins [2]. |
| ln Vivo | The effect of Cyclovirobuxine D, an active ingredient from Buxus microphylla, was investigated in the potential prevention of cardiac dysfunction in rats with congestive heart failure. Heart failure was induced by left coronary artery occlusion and verified using echocardiography. Cyclovirobuxine D was administered for 30 days (0.5, 1.0 and 2.0mg/kg, ig) and mortality, cardiac function, hemodynamics, microcirculation, histology and ultrastructure assessments were observed. Results from the present study suggest that Cyclovirobuxine D is beneficial for heart failure induced by myocardial infarction and supports the potential for Cyclovirobuxine D as a new therapy for heart failure.[3] |
| Cell Assay |
Cell Viability Assay[2] Cell Types: MGC-803 and MKN28 Cell Tested Concentrations: 0, 30, 60, 120 and 240 µM Incubation Duration: 24, 48, 72 hrs (hours) Experimental Results: diminished cell viability and colony-forming ability of gastric cancer cells during cell cycle Analysis[2] Cell Types: MGC-803 and MKN28 cells Tested Concentrations: 0, 30, 60 and 120 µM Incubation Duration: 48 hrs (hours) Experimental Results: Cell cycle progression of MGC-803 and MKN28 cells is arrested. Apoptosis analysis[2] Cell Types: MGC-803 and MKN28 Cell Tested Concentrations: 0, 30, 60 and 120 µM Incubation Duration: 48 hrs (hours) Experimental Results: Induction of apoptosis in MGC-803 and MKN28 cells. Western Blot Analysis[2] Cell Types: MGC-803 and MKN28 Cell Tested Concentrations: 0, 30, 60 and 120 µM Incubation Duration: 48 hrs (hours) Experimental Results: Up-regulation of cleaved Caspase-3 and Bax, and diminished expression of Bcl-2. |
| Animal Protocol |
Effect of CVB-D on survival rate[3] In the vehicle group, four rats died during the treatment period and the survival rate was 66.7%. The survival rate for the captopril and CVB-D (0.5, 1.0 and 2.0 mg/kg, ig) groups was 83.33%, 75.0%, 75.0% and 83.33% respectively. None of the sham-operated rats died during the experimental timeframe. The cause of death included acute heart failure, bleeding, serious arrhythmia, and respiratory failure. |
| Toxicity/Toxicokinetics | mouse LD50 oral 293 mg/kg |
| References |
[1]. Cyclovirobuxine D induces autophagy-associated cell death via the Akt/mTOR pathway in MCF-7 human breast cancer cells. J Pharmacol Sci. 2014;125(1):74-82. Epub 2014 Apr 24. [2]. Cyclovirobuxine D Inhibits Cell Proliferation and Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer Cells. Molecules. 2015 Nov 19;20(11):20659-68. [3]. Beneficial effect of Cyclovirobuxine D on heart failure rats following myocardial infarction. Fitoterapia. 2011 Sep;82(6):868-77. |
| Additional Infomation | Cyclovirobuxine D has been reported in Buxus microphylla and Buxus sempervirens with data available. |
Solubility Data
| Solubility (In Vitro) |
|
|||
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.08 mg/mL (2.68 mM) (saturation unknown) in 10% EtOH + 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 10.8 mg/mL clear EtOH stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 1.08 mg/mL (2.68 mM) (saturation unknown) in 10% EtOH + 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 10.8 mg/mL clear EtOH 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: ≥ 1.08 mg/mL (2.68 mM) (saturation unknown) in 10% EtOH + 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 10.8 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4835 mL | 12.4174 mL | 24.8348 mL | |
| 5 mM | 0.4967 mL | 2.4835 mL | 4.9670 mL | |
| 10 mM | 0.2483 mL | 1.2417 mL | 2.4835 mL |