Ацетилсульфаметоксазол

Description

Acetylsulfamethoxazole (N4-acetylsulfamethoxazole) is the main metabolite of the widely used antibiotic sulfamethoxazole. Formula C12H13N3O4S, CAS 21312-10-7, EC number 244-330-5, UNII 3I1988834Q, DSSTox ID DTXSID8049044, ATC code J01EC01, HS code 2935009090. Molecular weight 295.31, exact mass is 295.31. PSA specifications: 110; XLogP3: 0.86. Synonyms: N-[4-[[(5-methyl-3-isoxazolyl)amino]sulfonyl]phenyl]acetamide, 4'-acetyl-3-sulpha-5-methylisoxazole, STX 606.

Physico-chemical characteristics

• Density: 1.448 g/cm3
• Melting point: 220-221 °C
• Refractive index: 1.622
• Solubility in water: 76 mg/l (37 °C)
• Storage conditions: refrigerator
• Collision cross section: 171.45 Å2 [M+H]+; 178.52 Å2 [M+Na]+; 172.05 Å2 [M-H]-; 167.81 Å2 [M+H]+; 171.5 Å2 [M-H]- (CCS type: DT, method: step field)

Substance class and origin

Sulfamethoxazole (ATC code J01EC01) is a sulfonamide antibiotic, a dihydropteroate synthetase inhibitor, often used in combination with trimethoprim (co-trimoxazole) to treat a wide range of bacterial infections, including urinary tract infections and Pneumocystis pneumonia. In the liver, sulfamethoxazole is metabolized by acetylation by extramitochondrial N-acetyltransferases to form acetylsulfamethoxazole, which is excreted in the urine.

Genetics of acetylation

N4-acetylation of sulfamethoxazole is catalyzed by the polymorphic liver enzyme N-acetyltransferase 2 (NAT2), for which about 108 allelic variants have been described. According to the genotype, fast acetylators (two fast alleles), intermediate (one fast and one slow allele) and slow (two slow alleles) are distinguished. Slow acetylation is an established risk factor for adverse reactions to sulfonamide drugs: in such patients, hepatotoxicity and other undesirable effects of sulfonamides, including the skin reactions described for the sulfamethoxazole/trimethoprim combination, are more common and more severe.

General mechanism of action of sulfonamides

Sulfamethoxazole, like other sulfonamides, competitively inhibits the bacterial enzyme dihydropteroate synthetase, structurally imitating para-aminobenzoic acid (PABA), a precursor required by microbial cells for the synthesis of folic acid and, accordingly, nucleic acids. In combination with trimethoprim, which blocks the next enzyme in the same pathway, dihydrofolate reductase, a double sequential blockade of folate synthesis is achieved, which explains the synergism of co-trimoxazole. N4-acetylation, which produces the metabolite in question, eliminates the structural similarity of the molecule to PABA and completely inactivates the antibacterial activity.

Scope of application

In addition to its clinical significance as the main route for removing sulfamethoxazole from the body, the compound is used in biochemistry as an organic synthesis reagent that promotes the production of sulfonamides and amines, and also as a reference standard for the determination of N4-acetylsulfamethoxazole in biological fluids by high-performance liquid chromatography.

Storage conditions

Store in the refrigerator in a tightly closed container, protected from light and moisture.