| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Proguanil, also known as chlorguanide and chloroguanide, is a orally bioavailable medication used to treat and prevent malaria. It is an antimalarial prodrug that is metabolized to the active metabolite cycloguanil, a dihydrofolate reductase (DHFR) inhibitor. It is often used together with chloroquine or atovaquone. When used with chloroquine the combination will treat mild chloroquine resistant malaria. When used alone, proguanil functions as a prodrug. Its active metabolite, cycloguanil, is an inhibitor of dihydrofolate reductase (DHFR). Although both mammals and parasites produce DHFR, cycloguanil's inhibitory activity is specific for parasitic DHFR. This enzyme is a critical component of the folic acid cycle. Inhibition of DHFR prevents the parasite from recycling dihydrofolate back to tetrahydrofolate (THF). THF is required for DNA synthesis, amino acid synthesis, and methylation; thus, DHFR inhibition shuts down these processes.
| ln Vitro |
The antimalarial activity of proguanil in vitro is weak (IC50=2.4-19 μM), and its efficacy is dependent on cyclic guanidine, which is its active metabolite and has an IC50 of 0.5-2.5 nM. Dihydrofolate reductase (DHFR) is inhibited by cyclic guanidine. Synergy between proguanil and atovaquone is seen in vitro. Additionally, both medications are effective against Plasmodium at the gametocyte and preerythrocytic (liver) stages [1]. By functioning as a biguanide instead of its metabolite cycloguanidine, a parasite dihydrofolate reductase [DHFR] inhibitor, proguanil enhances the effects of atovaquone. Since proguanil does not change the effects of other mitochondrial electron transport inhibitors (such myxothiazole and antimycin), proguanil-mediated potentiation is limited to atovaquone [2]. With IC50s of 1.81, 1.48, and 4.36 μM, respectively, proguanil, the metabolite 4-chlorophenyl-1-biguanide (CPB), and the active metabolite cyclic guanidine (CG) reversibly block the 5-HT3 receptor response [3].
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| ln Vivo |
In Wistar strain albino rats, proguanil (oral; 2.9 mg/kg body weight; once daily for 5 days and 6 weeks) caused mild degenerative changes to last for 5 days and severe degenerative changes to last for 6 weeks. alterations[4]. Rats given proguanil showed a substantial decrease in serum testosterone levels [4]. When two chronic-phase and three acute-phase dogs experimentally infected with Bacillus gibbenii were given malarone (atovaquone and proguanil), parasitemia was decreased and clinical improvement was noted [5].
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| References |
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| Additional Infomation |
Proguanil Hydrochloride is the hydrochloride salt form of proguanil, a synthetic biguanide derivative of pyrimidine and an folate antagonist with antimalarial property. Upon hydrolysis, proguanil is converted to its active cyclic triazine metabolite, cycloguanil, by a cytochrome P450 dependent reaction. Cycloguanil selectively inhibits the bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS) of plasmodium parasite, thereby disrupting deoxythymidylate synthesis and ultimately blocking DNA and protein synthesis in the parasite.
A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent. See also: Proguanil (annotation moved to). |
| Molecular Weight |
290.19218
|
|---|---|
| Exact Mass |
289.086
|
| CAS # |
637-32-1
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| Related CAS # |
Proguanil;500-92-5;Proguanil-d6 hydrochloride;Proguanil-d6;Proguanil-d4 hydrochloride;1189671-34-8
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| PubChem CID |
9570076
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| Appearance |
Typically exists as solid at room temperature
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| Boiling Point |
402.7ºC at 760 mmHg
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| Melting Point |
249-251ºC
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| Flash Point |
197.4ºC
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| LogP |
4.065
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
1
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
18
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| Complexity |
292
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)N=C(N)/N=C(\N)/NC1=CC=C(C=C1)Cl.Cl
|
| InChi Key |
SARMGXPVOFNNNG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H16ClN5.ClH/c1-7(2)15-10(13)17-11(14)16-9-5-3-8(12)4-6-9/h3-7H,1-2H3,(H5,13,14,15,16,17)1H
|
| Chemical Name |
(1E)-1-[amino-(4-chloroanilino)methylidene]-2-propan-2-ylguanidinehydrochloride
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| Synonyms |
Proguanil HCl Paludrine Chloroguanide hydrochloride Chloroquanil
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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) |
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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.4460 mL | 17.2301 mL | 34.4602 mL | |
| 5 mM | 0.6892 mL | 3.4460 mL | 6.8920 mL | |
| 10 mM | 0.3446 mL | 1.7230 mL | 3.4460 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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