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Furagin (NF-416; Furazidin; F-35; Akritoin; Furazidine) is a potent anti-bacterial agent structurally similar to nitrofurantoin. It has the same efficacy in treating acute cystitis as ciprofloxacin, however the duration of therapy is longer.
Furagin (also known as suragin, furazidine) is a 2‑substituted 5‑nitrofuran antibacterial agent, chemically and structurally similar to nitrofurantoin. It is clinically used for the treatment of urinary tract infections (UTIs), particularly in some Eastern European countries, and may be administered as a long‑term low‑dose prophylaxis (e.g., 1–2 mg/kg/day for up to 12 months) in children with recurrent UTIs. In vitro, furagin acts as an isoform‑selective human carbonic anhydrase (hCA) inhibitor, showing potent activity against the tumor‑associated isoforms hCA IX and hCA XII (Ki = 260 nM and 57 nM, respectively), while poorly inhibiting off‑target hCA I and hCA II (Ki > 100 μM and 9.6 μM, respectively). In pediatric patients, long‑term oral treatment with furagin was associated with a time‑independent increase in sister chromatid exchange frequency and a time‑dependent increase in chromatid exchanges (triradials and quadriradials), indicating genotoxic effects. These findings suggest possible drug repurposing of furagin as an anticancer agent, but also raise concerns about its genetic safety with prolonged use.| Targets |
Human carbonic anhydrase (hCA) isoforms I, II, IX, and XII [3]
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| ln Vitro |
Furagin exhibited inhibitory activity against human carbonic anhydrase isoforms with the following Ki values: hCA I > 100,000 nM (no significant inhibition); hCA II = 9,600 nM (9.6 μM); hCA IX = 260 nM; hCA XII = 57 nM. It showed good selectivity for the tumor-associated isoforms hCA IX and XII over off-target hCA I and II. [3]
Molecular docking and 100 ns molecular dynamics simulations suggested that the selectivity of Furagin for CA IX/XII over CA II is due to strong hydrogen bond interactions in CA IX/XII, whereas in CA II the ligand tail orients towards a hydrophobic area and does not form persistent hydrogen bonds. The zinc-binding group (the negatively charged imidic nitrogen of the hydantoin nucleus) coordinates the zinc ion, and the oxygen atom of the carbonyl group at position 4 of the hydantoin core acts as a bifurcated acceptor forming two hydrogen bonds with Thr199. [3] |
| ln Vivo |
In pediatric patients with urinary tract infections, Furagin (referred to as suragin) was administered orally at a dose of 5–8 mg/kg/day for the first 7 days, followed by 1–2 mg/kg/day for up to 12 months. Blood samples were taken before, just after, and at 1, 3, 6, and 12 months of therapy. [2]
A time-independent increase in sister chromatid exchange (SCE) frequency was found in lymphocytes of children treated with Furagin. SCE per cell values were: before treatment 6.70 ± 0.20; after 1 month 8.26 ± 0.45 (P < 0.05); after 3 months 7.67 ± 1.13; after 6 months 7.37 ± 0.59; after 12 months 8.37 ± 0.36 (P < 0.05). Total chromosome aberration frequency did not differ significantly between groups with various treatment durations, but the frequency of chromatid exchanges (triradials and quadriradials) increased significantly with treatment duration (Y = 0.066 + 0.019X, r² = 0.83, where Y is the number of chromatid exchanges per 100 cells, X the duration in months). [2] Rogue cells (cells with multiple chromosome-type aberrations) were detected in 4 children: two before any treatment, one after 6 months, and one after 12 months of Furagin therapy. [2] |
| Enzyme Assay |
Carbonic anhydrase inhibition assay: An Applied Photophysics stopped-flow instrument was used for assaying the CA-catalyzed CO₂ hydration activity. The inhibition constants (Ki) were obtained by non-linear least-squares methods using PRISM 3 and the Cheng-Prusoff equation, representing the mean from at least three different determinations. The four tested CA isoforms (hCA I, II, IX, XII) were recombinant proteins. [3]
Molecular docking and molecular dynamics simulations: The crystal structures of CA II (pdb 5LIT), CA IX (pdb 5FL4) and CA XII (pdb 1JD0) were prepared using the Protein Preparation Wizard in Maestro. The imidic nitrogen of the hydantoin nucleus was considered negatively charged (deprotonated) in simulations. Docking was performed with Glide in standard precision mode. The best poses were refined with Prime using a VSGB solvation model, and then submitted to 100 ns molecular dynamics simulations using Desmond with OPLS3e force field. [3] |
| ADME/Pharmacokinetics |
A study was conducted to investigate the human pharmacokinetics of furagin, a nitrofurantoin congener. The research included two phases: a single oral administration of 200 mg, and a 9-day continuous treatment with a dosage of 100 mg three times daily (t.i.d.). Nitrofurantoin, administered at the same dose, was used as the reference drug.
During the acute cross-over phase, food significantly accelerated the absorption of furagin, while atropine slightly delayed it. However, the total absorption of furagin remained nearly unchanged, as evidenced by the unaltered area under the curve (AUC) values. Serum concentrations of furagin remained above the minimum inhibitory concentration (MIC) of many pathogenic bacteria for several hours.
Even though furagin reached high serum concentrations, its urinary levels were generally lower than those of nitrofurantoin. The 24-hour urinary recovery rates were 8–13% for furagin and approximately 36% for nitrofurantoin.
In the prolonged treatment trial, furagin was absorbed and excreted in a manner consistent with the acute phase. On the 9th day of continuous administration, serum and urinary concentrations of furagin were higher than those observed on the first day. Throughout the study, urinary concentrations of both furagin and nitrofurantoin remained well above the MIC values of the most susceptible bacteria.
A number of volunteers reported experiencing nightly calf cramps after taking furagin for several days; otherwise, the side effects associated with furagin were minimal. [1]
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| Toxicity/Toxicokinetics |
In pediatric patients treated with Furagin for up to 12 months, a significant time-independent increase in sister chromatid exchange frequency was observed, as well as a time-dependent increase in chromatid exchanges (triradials and quadriradials) with treatment duration. Rogue cells (cells with multiple chromosome-type aberrations) were detected in some treated patients. [2]
No acute toxicity or mutagenicity data are reported in these references; however, the authors note that previous studies showed furagin and nitrofurantoin have similar genotoxic potencies in vitro (Ames test, CA and SCE in human lymphocytes, Drosophila assays). [2] |
| References |
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| Additional Infomation |
Nitrofuran derivative anti-infective agents used to treat urinary tract infections.
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| Molecular Formula |
C10H8N4O5
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|---|---|
| Molecular Weight |
264.197
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| Exact Mass |
264.049
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| Elemental Analysis |
C, 45.46; H, 3.05; N, 21.21; O, 30.28
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| CAS # |
1672-88-4
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| Related CAS # |
1672-88-4;22060-47-5 (sodium);21287-44-5 (potassium);
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| PubChem CID |
6870646
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.6±0.1 g/cm3
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| Melting Point |
267-270ºC (dec.)
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| Index of Refraction |
1.689
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| LogP |
0.81
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
19
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| Complexity |
455
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1C(=O)NC(=O)N1/N=C/C=C/C2=CC=C(O2)[N+](=O)[O-]
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| InChi Key |
DECBQELQORZLLP-UAIOPKHMSA-N
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| InChi Code |
InChI=1S/C10H8N4O5/c15-8-6-13(10(16)12-8)11-5-1-2-7-3-4-9(19-7)14(17)18/h1-5H,6H2,(H,12,15,16)/b2-1+,11-5+
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| Chemical Name |
1-[(E)-[(E)-3-(5-nitrofuran-2-yl)prop-2-enylidene]amino]imidazolidine-2,4-dione
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| Synonyms |
NF-416; NF416; FURAGIN; Furazidine; 1672-88-4; Furazidin; Akritoin; NF 416
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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 : ~25 mg/mL (~94.63 mM)
H2O : < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (9.46 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7850 mL | 18.9251 mL | 37.8501 mL | |
| 5 mM | 0.7570 mL | 3.7850 mL | 7.5700 mL | |
| 10 mM | 0.3785 mL | 1.8925 mL | 3.7850 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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