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Cinoxacin (Cinobac; Compound 64716) was a synthetic antimicrobial agent for oral administration. It belongs to the quinolone class of antibiotics with activity similar to oxolinic acid and nalidixic acid. It was commonly used thirty years ago to treat urinary tract infections in adults. There are reports that cinoxacin had also been used to treat initial and recurrent urinary tract infections and bacterial prostatitis in dogs however this veterinary use was never approved by the FDA. In complicated UTI, the older gyrase-inhibitors such as cinoxacin are no longer indicated. It has been discontinued in the U.K. as well the United States, both as a branded drug or a generic. The marketing authorization of cinoxacin has been suspended throughout the EU.
Physicochemical Properties
| Molecular Formula | C12H10N2O5 |
| Molecular Weight | 262.2182 |
| Exact Mass | 262.058 |
| Elemental Analysis | C, 54.97; H, 3.84; N, 10.68; O, 30.51 |
| CAS # | 28657-80-9 |
| Related CAS # | Cinoxacin-d5;2732985-25-8 |
| PubChem CID | 2762 |
| Appearance | White to off-white solid powder |
| Density | 1.6±0.1 g/cm3 |
| Boiling Point | 517.2±60.0 °C at 760 mmHg |
| Melting Point | 210 °C |
| Flash Point | 266.6±32.9 °C |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.709 |
| LogP | 0.35 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 19 |
| Complexity | 449 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(C1=NN(CC)C2=C(C=C3C(OCO3)=C2)C1=O)O |
| InChi Key | VDUWPHTZYNWKRN-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C12H10N2O5/c1-2-14-7-4-9-8(18-5-19-9)3-6(7)11(15)10(13-14)12(16)17/h3-4H,2,5H2,1H3,(H,16,17) |
| Chemical Name | 1-Ethyl-1,4-dihydro-4-oxo[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid |
| Synonyms | Cinoxacin; Cinobac; Compound 64716; Cinoxacine; Cinoxacino; Cinoxacinum;Acid, Azolinic; Azolinic Acid; |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | Quinolone |
| ln Vitro | Many gram-negative aerobic bacteria are inhibited by cefoxacin (0-200μg/mL, approximately, 3-24 h), with MIC values ranging from 4 to 64 μg/mL[2]. |
| ln Vivo | With ED50 values ranging from 8.1 to 58.6 mg/kg, isoxacin (oral administration, 1.7 g/kg, treated at 1 and 5 h postinfection) is effective against experimental bacterial infections in mice[2]. |
| Cell Assay |
Cell Line: Gram-negative aerobic bacteria (Escherichia coli, Proteus sp. etc.) Concentration: 0-200μg/mL approximately Incubation Time: 3-24 h Result: reduced the number of cells (by 68% to 73%) at 40 and 60 μM and inhibited basal cell proliferation (40% in FB-2 and 35% in WRO) at 10 μM. |
| Animal Protocol |
Animal Model: Indicated bacterial infected mice model[2] Dosage: 1.7 g/kg, treated at 1 and 5 h postinfection Administration: Oral administration Result: demonstrated antibacterial activity, with a range of 81 to 58.6 mg/kg for the ED50 value. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Rapidly absorbed after oral administration. While concurrent food intake may delay the drug absorption, the total drug absorption is not affected. Metabolism / Metabolites Hepatic, with approximately 30-40% metabolized to inactive metabolites. Biological Half-Life While the mean serum half-life is 1.5 hours, the half-life may exceed 10 hours in case of renal impairment. |
| Toxicity/Toxicokinetics |
Protein Binding 60 to 80% |
| References |
[1]. Cinoxacin: mechanism of action, spectrum of activity, pharmacokinetics, adverse reactions, and therapeutic indications. Pharmacotherapy. 1982 Sep-Oct;2(5):266-72. [2]. Compound 64716, a new synthetic antibacterial agent. Antimicrob Agents Chemother. 1973 Oct;4(4):415-20. |
| Additional Infomation |
Cinoxacin is a member of the class of cinnolines that is 6,7-methylenedioxycinnolin-4(1H)-one bearing an ethyl group at position 1 and a carboxylic acid group at position 3. An analogue of oxolinic acid, it has similar antibacterial actions. It was formerly used for the treatment of urinary tract infections. It has a role as an antibacterial drug and an antiinfective agent. It is a member of cinnolines, an oxo carboxylic acid and an oxacycle. Synthetic antimicrobial related to oxolinic acid and nalidixic acid and used in urinary tract infections. Synthetic antimicrobial related to OXOLINIC ACID and NALIDIXIC ACID and used in URINARY TRACT INFECTIONS. Drug Indication For the treatment of initial and recurrent urinary tract infections in adults caused by the following susceptible microorganisms: Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species (including K. pneumoniae), and Enterobacter species. FDA Label Mechanism of Action Evidence exists that cinoxacin binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis. It appears to also inhibit DNA gyrase. This enzyme is necessary for proper replicated DNA separation. By inhibiting this enzyme, DNA replication and cell division is inhibited. Pharmacodynamics Cinoxacin is a synthetic antibacterial agent with in vitro activity against many gram-negative aerobic bacteria, particularly strains of the Enterobacteriaceae family. Cinoxacin inhibits bacterial deoxyribonucleic acid (DNA) synthesis, is bactericidal, and is active over the entire urinary pH range. Cross resistance with nalidixic acid has been demonstrated. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~8.33 mg/mL (~31.77 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8136 mL | 19.0680 mL | 38.1359 mL | |
| 5 mM | 0.7627 mL | 3.8136 mL | 7.6272 mL | |
| 10 mM | 0.3814 mL | 1.9068 mL | 3.8136 mL |