Warangalone is an isoflavonoid anti-malarial compound isolated from the insecticidal plant Derris scandens that acts as a powerful inhibitor of protein kinase A. It can inhibit the growth of both strains of parasite 3D7 (chloroquine sensitive) and K1 (chloroquine resistant) with IC50s of 4.8 μg/mL and 3.7 μg/mL, respectively. Warangalone can also inhibit cyclic AMP-dependent protein kinase catalytic subunit (cAK) with an IC50 of 3.5 μM.
Physicochemical Properties
| Molecular Formula | C25H24O5 |
| Molecular Weight | 404.45506 |
| Exact Mass | 404.162 |
| Elemental Analysis | C, 74.24; H, 5.98; O, 19.78 |
| CAS # | 4449-55-2 |
| Related CAS # | 2934.99.03.00 |
| PubChem CID | 5379679 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 627.0±55.0 °C at 760 mmHg |
| Flash Point | 216.7±25.0 °C |
| Vapour Pressure | 0.0±1.9 mmHg at 25°C |
| Index of Refraction | 1.628 |
| LogP | 7.87 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 30 |
| Complexity | 752 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C1C(C(O)=C(C=CC(C)(C)O2)C2=C3C/C=C(C)\C)=C3OC=C1C4=CC=C(O)C=C4 |
| InChi Key | HGHOPAZIUPORIN-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C25H24O5/c1-14(2)5-10-18-23-17(11-12-25(3,4)30-23)21(27)20-22(28)19(13-29-24(18)20)15-6-8-16(26)9-7-15/h5-9,11-13,26-27H,10H2,1-4H3 |
| Chemical Name | 5-hydroxy-7-(4-hydroxyphenyl)-2,2-dimethyl-10-(3-methylbut-2-en-1-yl)-2H,6H-pyrano[3,2-g]chromen-6-one |
| Synonyms | Warangalone; Scandenolone |
| 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 | Plasmodium |
| ln Vitro | Warangalone is an anti-malarial substance that has the ability to stop the growth of parasite strains 3D7, which is sensitive to chloroquine, and K1, which is resistant to it, with IC50 values of 4.8 μg/mL and 3.7 μg/mL, respectively[1]. With an IC50 of 3.5 μM, warangalone can also inhibit the catalytic subunit of cyclic AMP-dependent protein kinase (cAK)[2]. In comparison to controls, warangalone (30 μM) significantly reduces (8%) the viability of HL-60 cells after 24 hours of exposure. Additionally, warangalone exhibits time-dependent inhibition of HL-60 cell growth within 24 hours. After treating cells with warangalone, there is a time-dependent increase in caspase-9 activity[3]. |
| Enzyme Assay | The caspase fluorometric assay kit is used to measure the enzyme activities of caspase-3 and caspase-9. In 24-well plates, cells are seeded at a density of 3×106 cells per well. Following the designated duration of exposure to Warangalone, the cells undergo three PBS washes before being lysed for ten minutes on ice in a lysis buffer. Using a Micro BCA reagent, the protein content of the cell lysates is measured. 50 μg of protein-containing cell lysates are incubated for one hour at 37°C with either a caspase-9 fluorogenic substrate (LEHD-AFC) or a caspase-3 fluorogenic substrate (DEVD-AFC). Fluorometric detection is used to quantify caspase activity[3]. |
| Cell Assay | Cell Titer 96 Aqueous assay kit is used to determine cell viability. A density of 1×105 cells per well is seeded in 96-well plates. Following a 24-hour period at 37°C, 30 μM of warangalone is added to the culture medium. At the designated times, MTS solution is added to the 96-well plates, and the cells are then incubated for one hour at 37°C. A microplate counter is used to measure the absorbance at 490 nm in wavelength[3]. |
| References |
[1]. ANTI-MALARIAL COMPOUND FROM THE STEM BARK OF Erythrina variegate. Indo. J. Chem., 2009, 9 (2), 308-311. [2]. Specific inhibition of cyclic AMP-dependent protein kinase by warangalone and robustic acid. Phytochemistry. 1997 Mar;44(5):787-96. [3]. Induction of apoptosis by isoflavonoids from the leaves of Millettia taiwaniana in human leukemia HL-60 cells. Planta Med. 2006 Apr;72(5):424-9. |
| Additional Infomation | Warangalone has been reported in Maclura pomifera, Euchresta horsfieldii, and other organisms with data available. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4724 mL | 12.3622 mL | 24.7243 mL | |
| 5 mM | 0.4945 mL | 2.4724 mL | 4.9449 mL | |
| 10 mM | 0.2472 mL | 1.2362 mL | 2.4724 mL |