Trimethoprim (Synonyms: NIH 204, NSC 106568) |
Katalog-Nr.GC10137
One-Click Copy Product Info
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Trimethoprim ist ein bakteriostatisches Antibiotikum und ein oral wirksamer Dihydrofolat-Reduktase-Hemmer.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 738-70-5
Sample solution is provided at 25 µL, 10mM.
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Trimethoprim is a bacteriostatic antibiotic inhibiting dihydrofolate reductase (DHFR) enzyme activity. Trimethoprim selectively and reversibly inhibits bacterial DHFR, blocks the conversion of dihydrofolate to tetrahydrofolate, and interferes with bacterial nucleic acid and protein biosynthesis to exert antibacterial effects. Trimethoprim has antibacterial activity against susceptible Gram-positive aerobic cocci and Gram-negative aerobic bacilli such as Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter species and Staphylococcus saprophyticus. Trimethoprim is often used in combination with sulphamethoxazole to enhance antibacterial effects. Trimethoprim can be used for research and treatment of urinary tract infections, traveler's diarrhea, acute exacerbations of chronic bronchitis and Pneumocystis jirovecii pneumonia[1-4].
In vitro, treatment of peripheral blood lymphocytes with 25-50μg/mL Trimethoprim for 24-48 hours increased micronucleus frequency. Treatment of F2408 and 5RP7 cells with 5-200μM Trimethoprim for 24-72 hours inhibited cell proliferation and decreased mitochondrial activity[5]. Treatment of HCT116, RKO, DLD1, MCF7, 4T1, SUM159 and PyMT cells with 0.1-4mM Trimethoprim for 48 hours reduced cell viability and induced G1 phase arrest, downregulated cyclin D1, CDK4, CDK6 and phospho-Rb protein expression, decreased Snail protein level and promoted ubiquitination degradation, weakened Snail binding to CBP/p300 and Snail acetylation, elevated Snail phosphorylation level, increased E-cadherin and decreased vimentin, N-cadherin and fibronectin expression, and inhibited cell migration[6]. Treatment of foreskin fibroblasts co-cultured with Toxoplasma gondii 2F strain with 46μM Trimethoprim for 5 days inhibited tachyzoite growth[7].
In vivo, feeding white mice intraperitoneally inoculated with Toxoplasma gondii RH strain with food containing 2mg Trimethoprim and 1mg sulphamethoxazole for 20 days prolonged survival days of infected mice[8]. Intravenous injection of 25mg/kg Trimethoprim into Sprague-Dawley rats via jugular vein 15 minutes before intravenous injection of 1mg/kg emtricitabine decreased emtricitabine clearance, prolonged emtricitabine elimination half-life, increased apparent volume of distribution, and decreased renal excretion rate of emtricitabine[9]. Administration of 35mg/kg-70mg/kg Trimethoprim via drinking water to Swiss Webster mice intraperitoneally inoculated with Toxoplasma gondii RH strain for 13 days failed to eradicate Toxoplasma and did not improve mouse survival[10].
References:
[1] Gleckman R, Blagg N, Joubert DW. Trimethoprim: mechanisms of action, antimicrobial activity, bacterial resistance, pharmacokinetics, adverse reactions, and therapeutic indications. Pharmacotherapy. 1981 Jul-Aug;1(1):28-38.
[2] Rich G, Mee B. Trimethoprim. Med J Aust. 1985 Mar 18;142(6):350-2.
[3] Brogden RN, Carmine AA, Heel RC, et al. Trimethoprim: a review of its antibacterial activity, pharmacokinetics and therapeutic use in urinary tract infections. Drugs. 1982 Jun;23(6):405-30.
[4] Long MJC, Pan Y, Lin HC, et al. Cell Compatible Trimethoprim-Decorated Iron Oxide Nanoparticles Bind Dihydrofolate Reductase for Magnetically Modulating Focal Adhesion of Mammalian Cells. J Am Chem Soc. 2011 Jun 10;133(26):10006-10009.
[5] Guzel Bayülken D, Bostancioglu R B, Koparal A T, et al. Assessment of in vitro cytotoxic and genotoxic activities of some trimethoprim conjugates. Cytotechnology. 2018 Jun;70(3):1051-1059.
[6] Ren BX, Li Y, Li HM, et al. The antibiotic drug trimethoprim suppresses tumour growth and metastasis via targeting Snail. Br J Pharmacol. 2022 May;179(11):2659-2677.
[7] Hencken CP, Jones-Brando L, Bordon C, et al. Thiazole, Oxadiazole, and Carboxamide Derivatives of Artemisinin are Highly Selective and Potent Inhibitors of Toxoplasma gondii. J Med Chem. 2010 May 13;53(9):3594-3601.
[8] Sander J, Midtvedt T. The effect of trimethoprim on acute experimental toxoplasmosis in mice. Acta Pathol Microbiol Scand B. 1970;78(6):664-668.
[9] Nakatani-Freshwater T, Taft DR. Renal Excretion of Emtricitabine II. Effect of Trimethoprim on Emtricitabine Excretion: In Vitro and In Vivo Studies. J Pharm Sci. 2008 Dec;97(12):5411-5420.
[10] Dumas JL, Pizzolato G, Pechère JC. Evaluation of trimethoprim and sulphamethoxazole as monotherapy or in combination in the management of toxoplasmosis in murine models. Int J Antimicrob Agents. 1999 Jan;13(1):35-39.
| Cell experiment [1]: | |
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Cell lines |
HCT116, RKO, DLD1 cells (human colorectal carcinoma cell line), MCF7 cells (human breast adenocarcinoma cell line), SUM159 cells (human triple-negative breast cancer cell line), 4T1 cells, PyMT cells (mouse mammary tumor cell line) |
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Preparation Method |
Cells were maintained in DMEM or RPMI 1640 supplemented with 10% FBS at 37°C, 5% CO2. Cells were treated with Trimethoprim at 0.1-4mM for 48h. After treatment, cell viability was measured by CCK-8 and trypan blue/DAPI staining, apoptosis by Annexin V/PI flow cytometry, cell cycle by nocodazole synchronization and FACS, migration by transwell assay, and Snail/E-cadherin/vimentin/cyclin D1/CDK4/CDK6/p-Rb protein levels by immunoblotting. |
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Reaction Conditions |
0.1-4mM; 48h |
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Applications |
Trimethoprim dose-dependently reduced cell viability without inducing apoptosis or direct cell death in HCT116 and RKO cells. Trimethoprim decreased Snail protein levels and increased G1 phase cell fraction with reduced cyclin D1, CDK4, CDK6 and phospho-Rb expressions. Trimethoprim increased E-cadherin and decreased vimentin, N-cadherin and fibronectin levels, and inhibited cell migration in transwell assays. |
| Animal experiment [2]: | |
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Animal models |
White mice |
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Preparation Method |
Mice were intraperitoneally infected with 0.5mL of Toxoplasma gondii RH strain suspension (~7×10³ protozoans/mL). Simultaneously with infection, mice received daily per os treatment with Trimethoprim 2mg alone, sulphamethoxazole 2mg alone, or Trimethoprim 2mg combined with sulphamethoxazole 1mg for 10 or 20 days. Survival was recorded up to day 20 or day 30 post-inoculation. For carrier state testing, brain suspensions from surviving mice were injected intraperitoneally into four recipient mice, and peritoneal exudate or brain tissue was examined microscopically or by further mouse passage. |
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Dosage form |
2mg; p.o.; 10 or 20 days |
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Applications |
Trimethoprim 2mg alone showed no effect on survival of infected mice. Trimethoprim 2mg combined with sulphamethoxazole 1mg significantly prolonged survival compared with sulphamethoxazole 1mg alone. |
References: [1] Ren BX, Li Y, Li HM, et al. The antibiotic drug trimethoprim suppresses tumour growth and metastasis via targeting Snail. Br J Pharmacol. 2022;179(11):2659-2677. [2] Sander J, Midtvedt T. The effect of trimethoprim on acute experimental toxoplasmosis in mice. Acta Pathol Microbiol Scand B. 1970;78(6):664-8. | |
| Cas No. | 738-70-5 | SDF | |
| Überlieferungen | NIH 204, NSC 106568 | ||
| Chemical Name | 5-[(3,4,5-trimethoxyphenyl)methyl]pyrimidine-2,4-diamine | ||
| Canonical SMILES | COC1=CC(=CC(=C1OC)OC)CC2=CN=C(N=C2N)N | ||
| Formula | C14H18N4O3 | M.Wt | 290.32 |
| Löslichkeit | ≥ 12.25mg/mL in DMSO | Storage | Store at 2-8°C |
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4445 mL | 17.2224 mL | 34.4448 mL |
| 5 mM | 688.9 μL | 3.4445 mL | 6.889 mL |
| 10 mM | 344.4 μL | 1.7222 mL | 3.4445 mL |
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- Purity: >99.50% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)