Physicochemical Properties
| Molecular Formula | C37H40N2O6 |
| Molecular Weight | 608.7233 |
| Exact Mass | 608.288 |
| Elemental Analysis | C, 73.01; H, 6.62; N, 4.60; O, 15.77 |
| CAS # | 33889-68-8 |
| Related CAS # | Fangchinoline;436-77-1; 33889-68-8 |
| PubChem CID | 73481 |
| Appearance | White to off-white solid powder |
| Density | 1.2±0.1 g/cm3 |
| Boiling Point | 709.7±60.0 °C at 760 mmHg |
| Melting Point |
-245 °F to -148 °F 473 °F (decomposes) |
| Flash Point | 383.0±32.9 °C |
| Vapour Pressure | 0.0±2.3 mmHg at 25°C |
| Index of Refraction | 1.602 |
| Source | Stephania Tetrandra |
| LogP | 3.78 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 45 |
| Complexity | 963 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | O1C2=C(C([H])=C3C([H])([H])C([H])([H])N(C([H])([H])[H])C([H])(C([H])([H])C4C([H])=C([H])C(=C([H])C=4[H])OC4=C(C([H])=C([H])C(=C4[H])C([H])([H])C4([H])C5=C1C(=C(C([H])=C5C([H])([H])C([H])([H])N4C([H])([H])[H])OC([H])([H])[H])O[H])OC([H])([H])[H])C3=C2[H])OC([H])([H])[H] |
| InChi Key | IIQSJHUEZBTSAT-URLMMPGGSA-N |
| InChi Code | InChI=1S/C37H40N2O6/c1-38-14-12-24-19-31(42-4)33-21-27(24)28(38)16-22-6-9-26(10-7-22)44-32-18-23(8-11-30(32)41-3)17-29-35-25(13-15-39(29)2)20-34(43-5)36(40)37(35)45-33/h6-11,18-21,28-29,40H,12-17H2,1-5H3/t28-,29+/m0/s1 |
| Chemical Name | (11S,31R)-16,36,54-trimethoxy-12,32-dimethyl-11,12,13,14,31,32,33,34-octahydro-2,6-dioxa-1(7,1),3(8,1)-diisoquinolina-5(1,3),7(1,4)-dibenzenacyclooctaphan-37-ol |
| Synonyms | Fangchinoline; NSC 277171; NSC-277171; NSC277171; Isofangchinoline; Fangchinoline; Isofangchinoline; 33889-68-8; Demethyl tetrandrine; Limacine; 436-77-1; THALRUGOSINE; Thalrugosine;Thaligine; Thaligine; Thalrugosine; (+)-Limacine, 7-O-Demethyltetrandine; |
| 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: 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 | Natural product |
| ln Vitro |
With IC50 values of 19.0 µM (24 hours), 12.0 µM (48 hours), and 7.57 µM (5637 72 hours), 11.9 µM (24 hours), 9.92 µM (48 hours), and 7.13 µM (72 hours) in cells, fumangchinoline (2.5–40 µM; 24-96 hours) inhibits T24 and 5637 cells in a dose-dependent manner [1]. When applied to T24 and 5637 cells, fanchinoline (5 µM; 24 hours) significantly increases caspase-3 cleavage, decreases p62, and increases the ratio of LC3-II/LC3-I [1]. The introduction of highly active antiretroviral therapy has led to a significant reduction in the morbidity and mortality of acquired immunodeficiency syndrome patients. However, the emergence of drug resistance has resulted in the failure of treatments in large numbers of patients and thus necessitates the development of new classes of anti-HIV drugs. In this study, more than 200 plant-derived small-molecule compounds were evaluated in a cell-based HIV-1 antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (fangchinoline). Fangchinoline, a bisbenzylisoquinoline alkaloid isolated from Radix Stephaniae tetrandrae, exhibited antiviral activity against HIV-1 laboratory strains NL4-3, LAI and BaL in MT-4 and PM1 cells with a 50% effective concentration ranging from 0.8 to 1.7 µM. Mechanism-of-action studies showed that fangchinoline did not exhibit measurable antiviral activity in TZM-b1 cells but did inhibit the production of infectious virions in HIV-1 cDNA transfected 293T cells, which suggests that the compound targets a late event in infection cycle. Furthermore, the antiviral effect of fangchinoline seems to be HIV-1 envelope-dependent, as the production of infectious HIV-1 particles packaged with a heterologous envelope, the vesicular stomatitis virus G glycoprotein, was unaffected by fangchinoline. Western blot analysis of HIV envelope proteins expressed in transfected 293T cells and in isolated virions showed that fangchinoline inhibited HIV-1 gp160 processing, resulting in reduced envelope glycoprotein incorporation into nascent virions. Collectively, our results demonstrate that fangchinoline inhibits HIV-1 replication by interfering with gp160 proteolytic processing. Fangchinoline may serve as a starting point for developing a new HIV-1 therapeutic approach.[1] Fangchinoline effectively suppressed proliferation and invasion of A549 cell line but not NCI-H292, NCI-H446, and NCI-H460 cell lines by inhibiting the phosphorylation of FAK (Tyr397) and its downstream pathways, due to the significant differences of Fak expression between A549 and the other three cell lines. And all FAK-paxillin/MMP2/MMP9 pathway, FAK-Akt pathway, and FAK-MEK-ERK1/2 pathway could be inhibited by fangchinoline. Discussion: Fangchinoline effectively suppressed proliferation and invasion of A549 cell line by inhibiting the phosphorylation of FAK (Tyr397) and its downstream pathways. Conclusion: Fangchinoline could inhibit the phosphorylation of FAK(p-Tyr397), at least partially. Fangchinoline as a kinase inhibitor targets FAK and suppresses FAK-mediated signaling pathway and inhibits the growth and the invasion in tumor cells which highly expressed FAK such as A549 cell line. Keywords: FAK; fangchinoline; lung cancer cell; phosphorylation; signaling pathway.[2] Our data indicated that Fangchinoline/Fcn caused an impairment in energy generation, which led to apoptosis and adaptive autophagy in bladder cancer. These results demonstrated that Fcn may be a potential candidate for use in the prevention and treatment of bladder cancer.[3] |
| Cell Assay |
Cell Viability Assay[3] Cell Types: T24 and 5637 Cell Tested Concentrations: 2.5 µM; 5 µM; 10 µM; 20 µM; 30 µM; 40 µM Incubation Duration: 24 hrs (hours); 48 hrs (hours); 96 hrs (hours) Experimental Results: Inhibition of T24 and 5637 cell proliferation . Western Blot Analysis[3] Cell Types: T24 and 5637 Cell Tested Concentrations: 5 µM Incubation Duration: 24 hrs (hours) Experimental Results: Increased LC3-II/LC3-I ratio and caspase-3 cleavage. |
| References |
[1]. Fangchinoline inhibits human immunodeficiency virus type 1 replication by interfering with gp160 proteolytic processing. PLoS One. 2012;7(6):e39225. [2]. Fangchinoline as a kinase inhibitor targets FAK and suppresses FAK-mediated signaling pathway in A549. J Drug Target. 2015 Apr;23(3):266-74. [3]. Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer. Cell Physiol Biochem. 2017;43(3):1003-1011. |
| Additional Infomation |
Fangchinoline is a bisbenzylisoquinoline alkaloid that is (1beta)- berbaman which has been substituted by methyl groups at the 2 and 2' positions, by methoxy groups at the 6, 6', and 12 positions, and by a hydroxy group at position 7. Isolated from Stephania tetrandra, it has been found to possess neuroprotective and anti-tumour activity. It has a role as an antineoplastic agent, an anti-inflammatory agent, an antioxidant, an anti-HIV-1 agent, a neuroprotective agent and a plant metabolite. It is a macrocycle, a bisbenzylisoquinoline alkaloid and an aromatic ether. Fangchinoline has been reported in Stephania tetrandra, Stephania hernandifolia, and other organisms with data available. |
Solubility Data
| Solubility (In Vitro) |
DMSO : 50~100 mg/mL (82.14~164.27 mM) Ethanol : 5 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.11 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 25.0 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: ≥ 2.5 mg/mL (4.11 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 3: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (4.11 mM) (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6428 mL | 8.2140 mL | 16.4279 mL | |
| 5 mM | 0.3286 mL | 1.6428 mL | 3.2856 mL | |
| 10 mM | 0.1643 mL | 0.8214 mL | 1.6428 mL |