Acetohydroxamic Acid

Acetohydroxamic acid (AHA, CAS No. 546-88-3) is an irreversible urease inhibitor and a hydroxyurea derivative that targets bacterial and plant ureases. It is mainly used in research on chronic urinary tract infections, urease-related stones (struvite, magnesium ammonium phosphate stones), and Helicobacter pylori infection. AHA can also inhibit arachidonic acid 5‑lipoxygenase, reduce the formation of advanced glycation end products (AGEs), scavenge free radicals, and shows antiviral activity against HIV as well as antioxidant and anti-inflammatory effects.

In vitro, AHA can inhibit the formation of struvite crystals by Proteus mirabilis in artificial urine and inhibit the growth of H. pylori (MIC for different strains approximately 200–400 mg/L). In cell-based experiments, AHA (approximately 7 mM, incubated for 24 h) can enter bacterial cells, inhibit H. pylori urease activity, and reduce its adhesion to gastric tissue, thereby exerting antibacterial effects. AHA can also significantly reduce AGE formation under conditions of 2.5–5 mM for 10–14 days, scavenge DPPH and hydroxyl radicals within the range of 6 μM–50 mM for 30 min, and noncompetitively inhibit semicarbazide-sensitive amine oxidase (SSAO) under conditions of 0–50 μM for 1 min.

In canine models, long-term administration of AHA dose-dependently reduces urinary urease activity, pH, and crystallization, and significantly inhibits bladder stone formation; in P. mirabilis-associated urinary stone models, it can promote stone dissolution and reduce recurrence. In a Mongolian gerbil model of H. pylori gastritis, administration of AHA (reported dose approximately 2500 ppm/animal in feed) can markedly reduce the severity of gastritis and the gastric bacterial load. AHA-containing formulations have been used in therapeutic studies of chronic urinary tract infections associated with urease-positive bacteria and magnesium ammonium phosphate stones, and AHA is an important tool compound for exploring urease-targeted therapy, antioxidant/anti-inflammatory effects, and anti-HIV mechanisms.

References:

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[8] Liu YH, Lu YL, Liu DZ, Hou WC. Antiglycation, radical scavenging, and semicarbazide-sensitive amine oxidase inhibitory activities of acetohydroxamic acid in vitro. Drug Des Devel Ther. 2017 Jul 13;11:2139-2147. doi: 10.2147/DDDT.S141740. PMID: 28761331; PMCID: PMC5516777.