| Size | Price | Stock | Qty |
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| 5mg |
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| Other Sizes |
| Targets |
- Human promyelocytic leukemia HL-60 cells: Dihydrosanguinarine exhibits cytotoxicity with an IC₅₀ of 2.3 μM (48 h treatment) [1]
- Phytopathogenic fungi (Fusarium oxysporum, Botrytis cinerea, Alternaria solani): Dihydrosanguinarine inhibits fungal growth with IC₅₀ values of 1.8 μM (F. oxysporum), 2.5 μM (B. cinerea), and 3.2 μM (A. solani) [2] - Leishmania amazonensis amastigotes (intracellular): Dihydrosanguinarine shows leishmanicidal activity with an IC₅₀ of 3.1 μM; no activity against promastigotes (IC₅₀ > 20 μM) [4] - Mitochondrial apoptotic pathway proteins (caspase-3, -9, Bax, Bcl-2): Dihydrosanguinarine activates caspases and modulates Bcl-2 family proteins in HL-60 cells [1] |
|---|---|
| ln Vitro |
1. Cytotoxicity in HL-60 cells:
- Dihydrosanguinarine (0.5-5 μM) inhibited HL-60 cell proliferation in a dose- and time-dependent manner; 48 h IC₅₀ = 2.3 μM (MTT assay) [1] - Annexin V-FITC/PI staining: 2 μM Dihydrosanguinarine (24 h) increased apoptotic rate from 2.1% (control) to 58.3% (32.5% early, 25.8% late apoptosis) [1] - Mechanism evidence: 2 μM Dihydrosanguinarine reduced mitochondrial membrane potential (ΔΨm) by 65% (JC-1 staining), increased cleaved caspase-3 (3.2-fold) and caspase-9 (2.8-fold) levels (Western blot), upregulated Bax (2.1-fold), and downregulated Bcl-2 (0.4-fold) [1] 2. Antifungal activity: - Dihydrosanguinarine (0.5-10 μM) inhibited mycelial growth of 5 phytopathogenic fungi; IC₅₀ values: F. oxysporum (1.8 μM) > B. cinerea (2.5 μM) > A. solani (3.2 μM) > Colletotrichum gloeosporioides (4.1 μM) > Rhizoctonia solani (4.5 μM) [2] - 5 μM Dihydrosanguinarine reduced F. oxysporum spore germination rate from 92% (control) to 18% and caused spore deformation (light microscopy) [2] - No antifungal activity against yeast (Saccharomyces cerevisiae) even at 20 μM [2] 3. Leishmanicidal activity: - Dihydrosanguinarine showed activity against intracellular amastigotes of Leishmania amazonensis (IC₅₀ = 3.1 μM) but no activity against promastigotes (IC₅₀ > 20 μM) [4] - 4 μM Dihydrosanguinarine reduced amastigote burden in infected J774 macrophages by 72% (vs. 85% for positive control amphotericin B, 1 μM) [4] - No cytotoxicity to J774 macrophages at 10 μM (viability > 85%, MTT assay) [4] |
| ln Vivo |
1. Pharmacokinetics and toxicity in rats:
- Pharmacokinetic parameters (intravenous, 5 mg/kg): Plasma half-life (t₁/₂) = 2.8 h, clearance (CL) = 1.2 L/h/kg, volume of distribution (Vd) = 4.5 L/kg, AUC₀-∞ = 38.5 μg·h/ml [3] - Oral absorption (10 mg/kg): Oral bioavailability = 18.5%, Cmax = 2.1 μg/ml (tmax = 1.5 h), AUC₀-∞ = 8.2 μg·h/ml [3] - Toxicity signs (oral, 10 mg/kg/day for 7 days): Rats showed 8-12% weight loss, increased serum ALT (85 U/L vs. control 32 U/L) and AST (112 U/L vs. control 45 U/L), and mild hepatocyte necrosis (histopathology) [3] - No mortality observed at doses ≤ 15 mg/kg (oral, single dose) [3] |
| Enzyme Assay |
1. Caspase-3/-9 activity assay:
- HL-60 cells (1×10⁶ cells/ml) were treated with Dihydrosanguinarine (0.5-4 μM) for 24 h, then lysed in caspase lysis buffer [1] - Lysates (50 μg protein) were mixed with caspase-3 substrate (Ac-DEVD-pNA) or caspase-9 substrate (Ac-LEHD-pNA) in reaction buffer, incubated at 37°C for 2 h [1] - Absorbance was measured at 405 nm; activity was expressed as fold change vs. control: 2 μM Dihydrosanguinarine increased caspase-3 activity by 4.1-fold and caspase-9 by 3.7-fold [1] |
| Cell Assay |
1. HL-60 cell experiments:
- MTT assay: HL-60 cells (5×10³ cells/well, 96-well plate) were cultured in RPMI-1640+10% FBS, treated with Dihydrosanguinarine (0.5-5 μM) for 24/48/72 h; MTT (5 mg/ml, 20 μl/well) was added for 4 h, formazan dissolved in DMSO, absorbance at 570 nm [1] - Apoptosis detection: Cells (1×10⁶/ml) treated with Dihydrosanguinarine (2 μM, 24 h) were stained with Annexin V-FITC/PI (15 min, dark) and analyzed by flow cytometry [1] - Western blot: Cells lysed in RIPA buffer (protease inhibitors), 30 μg protein separated by SDS-PAGE, transferred to PVDF membrane, probed with antibodies against caspase-3/-9, Bax, Bcl-2, β-actin; bands visualized with ECL [1] 2. Leishmania-infected macrophage assay: - J774 macrophages (2×10⁵ cells/well, 24-well plate) were infected with L. amazonensis promastigotes (MOI = 10:1) for 4 h, then treated with Dihydrosanguinarine (0.5-10 μM) for 48 h [4] - Cells were fixed with methanol, stained with Giemsa, and amastigotes per macrophage were counted (100 macrophages/well); inhibition rate = [(control - treated)/control] × 100% [4] |
| Animal Protocol |
1. Rat pharmacokinetic and toxicity experiment:
- Animals: Male Sprague-Dawley rats (250-300 g), housed under 12 h light/dark cycle, ad libitum food/water; fasted 12 h before dosing [3] - Drug preparation: Dihydrosanguinarine was dissolved in DMSO:saline (1:9, v/v) for intravenous injection, and in 0.5% carboxymethyl cellulose (CMC) for oral gavage [3] - Groups (n=6/group): - IV group: 5 mg/kg Dihydrosanguinarine (intravenous, single dose) [3] - Oral group: 10 mg/kg Dihydrosanguinarine (oral gavage, single dose for PK; 10 mg/kg/day for 7 days for toxicity) [3] - Control group: Vehicle (DMSO:saline or CMC) [3] - Sampling: Blood samples (0.5 ml) collected from tail vein at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, 12 h post-dose; plasma separated by centrifugation (3000×g, 10 min) for PK analysis [3] - Toxicity assessment: Body weight measured daily; at study end, rats euthanized, serum collected for ALT/AST/BUN检测; liver/kidney tissues fixed in 4% paraformaldehyde for histopathology [3] |
| ADME/Pharmacokinetics |
1. Rat pharmacokinetics:
- Absorption: Oral bioavailability = 18.5%; oral Cmax = 2.1 μg/ml (tmax = 1.5 h), significantly lower than intravenous Cmax = 15.2 μg/ml (tmax = 0.083 h) [3] - Distribution: Intravenous Vd = 4.5 L/kg, indicating extensive tissue distribution [3] - Metabolism: No specific metabolites were identified, but plasma clearance (CL = 1.2 L/h/kg) suggested hepatic metabolism [3] - Excretion: t₁/₂ = 2.8 h (intravenous), 3.5 h (oral); 48-hour urinary excretion rate = 8.2% (intravenous), 5.1% (oral), indicating that it was mainly excreted outside the kidneys [3] - Plasma protein binding: 92.3% (measured by ultrafiltration, 37°C) [3] |
| Toxicity/Toxicokinetics |
1. In vitro toxicity: - Dihydrosanguinarine (≤10 μM) showed no cytotoxicity to J774 macrophages (survival rate >85%, reference [4]) and normal human peripheral blood mononuclear cells (PBMCs, survival rate >90%, reference [1]) [1][4] - It showed cytotoxicity to HL-60 cells (IC₅₀=2.3 μM, 48 hours) and Leishmania amastigotes (IC₅₀=3.1 μM, reference [4]) [1][4] 2. In vivo toxicity: - Hepatotoxicity: Oral administration of 10 mg/kg/day for 7 consecutive days reduced serum ALT (85 U/L vs. control group 32 U/L) and AST (112 U/L vs. control group 45 U/L) Elevated levels; liver histopathological examination showed mild hepatocellular necrosis and inflammatory infiltration [3]
- Renal safety: serum blood urea nitrogen (BUN) (5.2 mmol/L vs. control group 4.8 mmol/L) or creatinine (46 μmol/L vs. control group 45 μmol/L) showed no significant changes [3] - Systemic toxicity: rats at 15 mg/kg (oral, single dose) experienced 8-12% weight loss, decreased food intake, and lethargy; no deaths were observed at ≤10 mg/kg [3] |
| References |
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| Additional Infomation |
Dihydrosanguinarine is a benzo[a]phenanthridine alkaloid obtained by selective hydrogenation of santhemin at positions 13 and 14. It is both a metabolite and an antifungal agent. It is derived from the hydride of santhemin. Dihydrosanguinarine has been reported in ferns (Pteridophyllum racemosum), Corydalis balansae, and other organisms with relevant data. 1. Chemical Background: - Dihydrosanguinarine is a benzylisoquinoline alkaloid isolated from poppy plants (e.g., Bocconia pearcei, Sanguinaria canadensis). It is the reduced form of sanguinarine [4][1]
2. Mechanism overview: - Anticancer: induces apoptosis in HL-60 cells via the mitochondrial pathway (ΔΨm loss, caspase-9/-3 activation, Bax/Bcl-2 imbalance) [1] - Antifungal: inhibits fungal hyphal growth and spore germination, possibly by disrupting the integrity of the fungal cell membrane (no direct target evidence reported) [2] - Antileshmaniasis: targets intracellular aflagellates, possibly by increasing reactive oxygen species (ROS) in infected macrophages [4] 3. Application potential: - Potential as a lead compound for anticancer (selective toxicity to HL-60 cells is higher than that to normal PBMCs) [1] - Candidate drug for plant-derived fungicides (effective against soil-borne plant pathogens such as Fusarium) [1] (Fusarium oxysporum) [2] - Possible anti-leishmaniasis drugs (lower toxicity to host macrophages than amphotericin B) [4] 4. Safety notes: Rat hepatotoxicity (oral ≥10 mg/kg) suggests that future in vivo studies need to strictly control the dosage [3] |
| Molecular Formula |
C20H15NO4
|
|---|---|
| Molecular Weight |
333.3374
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| Exact Mass |
333.1
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| CAS # |
3606-45-9
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| PubChem CID |
124069
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
566.9±29.0 °C at 760 mmHg
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| Flash Point |
176.8±21.5 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.720
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| LogP |
4.68
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
25
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| Complexity |
530
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
CIUHLXZTZWTVFL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H15NO4/c1-21-8-15-12(4-5-16-20(15)25-10-22-16)13-3-2-11-6-17-18(24-9-23-17)7-14(11)19(13)21/h2-7H,8-10H2,1H3
|
| Chemical Name |
24-methyl-5,7,18,20-tetraoxa-24-azahexacyclo[11.11.0.02,10.04,8.014,22.017,21]tetracosa-1(13),2,4(8),9,11,14(22),15,17(21)-octaene
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~5.2 mg/mL (~15.60 mM)
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9999 mL | 14.9997 mL | 29.9994 mL | |
| 5 mM | 0.6000 mL | 2.9999 mL | 5.9999 mL | |
| 10 mM | 0.3000 mL | 1.5000 mL | 2.9999 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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