Acetohydroxamic acid
[CAS# 546-88-3]

Identification

• Classification: API >> Urinary system medication >> Other urinary system medication
• Name: Acetohydroxamic acid
• Synonyms: N-hydroxyacetamide
• Molecular Formula: C₂H₅NO₂
• Molecular Weight: 75.07
• CAS Registry Number: 546-88-3
• EC Number: 208-913-8
• SMILES: CC(=O)NO

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Melting point: 88 - 90 °C (Expl.)
• Boiling point: 231.4±23.0 °C 760 mmHg (Calc.)^*
• Flash point: 127.6±11.9 °C (Calc.)^*
• Solubility: 10 mM (H2O) (Expl.)
• Index of refraction: 1.437 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Danger
• Risk Statements: H360
• Safety Statements: P203-P280-P318-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Reproductive toxicity	Repr.	1B	H360

Discovery and Applications

Acetohydroxamic acid is an organic compound with the molecular formula CH₃CONHOH, consisting of an acetyl group bonded to a hydroxamic acid moiety. It is a white to off-white crystalline solid, soluble in water and polar organic solvents. The compound belongs to the class of hydroxamic acids, characterized by the presence of the functional group –CONHOH, which can chelate metal ions and inhibit certain enzymes. Acetohydroxamic acid has been used primarily in clinical medicine for the treatment of urinary tract infections (UTIs), particularly those associated with urease-producing bacteria.

The development of acetohydroxamic acid for medical use dates to the mid-20th century, when researchers sought compounds capable of inhibiting bacterial urease, an enzyme that catalyzes the hydrolysis of urea into ammonia and carbon dioxide. Infections caused by urease-producing organisms, such as *Proteus mirabilis*, can lead to the alkalinization of urine, which promotes the formation of struvite and apatite kidney stones. Acetohydroxamic acid was found to be a potent urease inhibitor, capable of preventing the increase in urinary pH and the crystallization of these compounds.

The drug has been used in patients with chronic urinary tract infections, especially those with indwelling catheters or structural abnormalities that predispose them to infection and stone formation. By inhibiting bacterial urease, acetohydroxamic acid reduces the production of ammonia in urine, helping to maintain a more acidic environment and thereby inhibiting the formation of infection-related stones. This makes it particularly valuable in managing cases of struvite urolithiasis.

Pharmacokinetically, acetohydroxamic acid is well absorbed from the gastrointestinal tract following oral administration, with peak plasma concentrations typically occurring within one to two hours. It is partially metabolized in the liver and excreted primarily via the kidneys. The plasma half-life is approximately 3 to 6 hours in patients with normal renal function, but elimination may be prolonged in individuals with renal impairment.

Clinically, acetohydroxamic acid has been marketed under trade names such as Lithostat and is prescribed for long-term use in patients who require suppression of urease activity. It is generally used as an adjunct to antimicrobial therapy and not as a substitute for antibiotics. Periodic monitoring of renal function and complete blood counts is recommended during therapy, particularly in long-term use.

Despite its effectiveness, acetohydroxamic acid is associated with several potential adverse effects. Common side effects include headache, rash, gastrointestinal disturbances, and dizziness. More serious but less frequent effects include thrombophlebitis, hemolytic anemia, methemoglobinemia, and neurotoxicity. Due to its side effect profile, its use is reserved for patients with persistent or complicated urinary infections not adequately managed by other means.

Beyond its medical application, acetohydroxamic acid has also been studied in biochemical research for its metal-chelating properties and as an inhibitor of other metalloenzymes. Its ability to coordinate with metal ions has led to its use as a ligand in coordination chemistry studies and as a model compound in enzymology.

In summary, acetohydroxamic acid is a hydroxamic acid derivative used in the management of chronic urinary tract infections caused by urease-producing bacteria. Its primary mode of action is the inhibition of bacterial urease, which helps prevent the formation of infection-related kidney stones. While effective, its use is limited to specific clinical scenarios due to the risk of adverse effects and the need for careful monitoring during therapy.

References

2024. International Alliance of Urolithiasis (IAU) guideline on staghorn calculi management. World Journal of Urology, 42(3).
DOI: 10.1007/s00345-024-04816-6

2023. Synthesis and modification of slow-release fertilizers for sustainable agriculture and environment: a review. Arabian Journal of Geosciences, 16(8).
DOI: 10.1007/s12517-023-11614-8