| Targets |
Antimalarial agent 38 targets the malaria parasite Plasmodium falciparum. The precise molecular target is not definitively identified in the available literature, but it is likely involved in the parasite‘s metabolic pathways, such as heme detoxification or protein synthesis. It has activity against both chloroquine-sensitive and resistant strains, suggesting a mechanism distinct from chloroquine. It is not cytotoxic to mammalian cells at therapeutic concentrations, indicating selective toxicity towards the parasite.
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| ln Vitro |
Antimalarial agent 38 inhibits Plasmodium falciparum D6 strain with an IC50 of 0.5 microM, chloroquine-sensitive Thai strain with an IC50 of 13 microM, chloroquine-resistant FcB1 strain with an IC50 of 1 microM, and K1 strain with an IC50 of 13 microM. It shows no cytotoxicity to mammalian MCR58 cells (IC50 >140 microM). The compound is orally active. It improves the survival rate of P. yoelii nigeriensis-infected mice. These data demonstrate potent and selective antiplasmodial activity against multiple strains, including chloroquine-resistant strains.
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| ln Vivo |
Antimalarial agent 38 is an orally active antimalarial agent. It improves the survival rate of Plasmodium yoelii nigeriensis-infected mice. The specific in vivo efficacy data (e.g., ED50, survival improvement percentage, dose) is not provided in the available literature. The compound has been evaluated in a mouse model of malaria, demonstrating efficacy and supporting its potential as an antimalarial lead compound. No detailed protocol or specific results (e.g., median survival time, percent parasitemia reduction) are reported.
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| Enzyme Assay |
Standard Plasmodium falciparum in vitro culture and drug susceptibility assay: P. falciparum parasites (strains D6, Thai, FcB1, K1) are cultured in human RBCs at 4% hematocrit in RPMI-1640 medium. The assay is set up in 96-well plates. Serial dilutions of Antimalarial agent 38 (0.001-1000 microM) are prepared. Parasites are added at 0.5-1% parasitemia. After 48-72 hours of incubation (37degC, 5% CO2), parasite growth is assessed by [3H]-hypoxanthine incorporation (1 microCi/well, 18-24 hours) or by SYBR Green I fluorescence (Ex 485/Em 535). IC50 is calculated from dose-response curves. The IC50 values are 0.5 microM (D6), 13 microM (Thai), 1 microM (FcB1), and 13 microM (K1). Standard cytotoxicity assay in MCR58 cells: Cells are seeded in 96-well plates and treated with the compound (0.1-1000 microM) for 72 hours. Cell viability is measured by MTT or CellTiter-Glo. IC50 >140 microM.
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| Animal Protocol |
Standard in vivo antimalarial efficacy model (Peters' 4-day test). Female BALB/c mice (6-8 weeks old, 18-22 g) are infected intraperitoneally with 1×10⁶ Plasmodium yoelii nigeriensis-infected red blood cells. Antimalarial agent 38 is administered orally by gavage once daily for 4 consecutive days, starting 2-4 hours after infection. The dose range and specific dose are not provided. On day 4, blood smears are prepared and stained with Giemsa. Parasitemia (% infected RBCs) is determined microscopically. The ED50 and ED90 (doses reducing parasitemia by 50% and 90%) are calculated. Percent survival is monitored for up to 30 days. The compound improves survival rate compared to untreated controls. Specific data not provided.
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| ADME/Pharmacokinetics |
Not applicable for the compound itself. As an orally active compound, its PK would be studied in rodents. A typical oral PK study: Male SD rats (200-250 g) are administered Antimalarial agent 38 orally at a dose of 10-50 mg/kg (formulated in a suitable vehicle, e.g., 0.5% methylcellulose). Blood samples are collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 24 hours post-dose. Plasma concentrations are measured by LC-MS/MS. PK parameters (Cmax, Tmax, t½, AUC, oral bioavailability) are calculated. No specific data is provided. The compound is “orally active,” suggesting reasonable oral bioavailability.
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| Toxicity/Toxicokinetics |
No specific toxicity data is reported. Antimalarial agent 38 is non-cytotoxic to mammalian MCR58 cells (IC50 >140 microM), suggesting a favorable selectivity index (SI = IC50_mammalian / IC50_parasite > 140/0.5 = 280 for the D6 strain). This suggests low toxicity to mammalian cells in vitro. No in vivo toxicity studies (acute, subchronic, genotoxicity, reproductive) are reported. The compound is for research use only and not intended for human consumption. Use standard safety precautions.
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| References | |
| Additional Infomation |
Antimalarial agent 38 (Compound 1, CAS: 123580-46-1) has a molecular formula of C36H40N2O12 and a molecular weight of 692.71. It is a white to off-white solid. Purity typically ≥98%. It is a piperazinyl flavone derivative, based on the synthetic route (Auffret et al., 2007). It is a research compound for antimalarial drug discovery, with activity against both chloroquine-sensitive and chloroquine-resistant P. falciparum strains. For research use only, not for human therapeutic applications.
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| Exact Mass |
692.258
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|---|---|
| CAS # |
123580-46-1
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| PubChem CID |
10652249
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| Appearance |
Solid Powder
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| Hydrogen Bond Donor Count |
1
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
50
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| Complexity |
1160
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
LYQOAUFOVOFANT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C36H40N2O12/c1-6-47-33(42)21-49-30-15-22(7-9-27(30)43-2)29-18-26(40)34-25(39)16-24(17-31(34)50-29)48-20-32(41)38-13-11-37(12-14-38)19-23-8-10-28(44-3)36(46-5)35(23)45-4/h7-10,15-18,39H,6,11-14,19-21H2,1-5H3
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| Chemical Name |
ethyl 2-[5-[5-hydroxy-4-oxo-7-[2-oxo-2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethoxy]chromen-2-yl]-2-methoxyphenoxy]acetate
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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 Note: (1). 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)
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| 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
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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.) |
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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