Sulfapyridine targets the bacterial enzyme dihydropteroate synthetase (DHPS), acting as a competitive inhibitor. By competing with the natural substrate para-aminobenzoic acid (PABA), it prevents the incorporation of PABA into dihydrofolic acid, the immediate precursor of folic acid. This inhibition disrupts the synthesis of folic acid, which is essential for bacterial growth and replication. Sulfapyridine inhibits recombinant P. carinii dihydropteroate synthetase with an IC50 of 0.18 µM. Beyond its antibacterial target, sulfapyridine also exhibits anti-inflammatory effects, including the inhibition of IL-8, CXCL1, and MCP-1 production in synovial cells of rheumatoid arthritis patients.

In rheumatoid arthritis (RA) synoviocytes, sulfapyridine suppresses the synthesis of IL-8, chemokine (CXC motif) ligand 1 (CXCL1), and monocyte chemoattractant protein 1 (MCP-1)[1]. Sulfapyridine has a minimum inhibitory concentration (MIC) range of 3.1–25 μg/mL for Yersinia enterocolitica and 25–100 μg/mL for Salmonella. Salmonella jejuni/E. Sulfapyridine has a lower susceptibility to coli, with MIC values ranging from 200 to 800 μg/mL. Three of the five E. Coli and Shigella. Sulfapyridine at 1600 μg/mL did not affect the coli strains. For two E, 25 μg/mL inhibits. strains of Coli [2].
Sulfapyridine demonstrates potent antibacterial activity by inhibiting recombinant P. carinii dihydropteroate synthetase (DHPS) with an IC50 of 0.18 µM. It is a sulfonamide antibiotic agent with a broad spectrum of activity against various bacteria. In addition to its antibacterial effects, sulfapyridine exhibits significant anti-inflammatory activity. It inhibits the production of IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1), and monocyte chemotactic protein-1 (MCP-1) in synovial cells of rheumatoid arthritis patients. This anti-inflammatory property contributes to its therapeutic efficacy in treating autoimmune conditions such as dermatitis herpetiformis and rheumatoid arthritis. Sulfapyridine has also been shown to inhibit mast cell-mediated immediate-type allergic reactions.

In rats, compound 48/80 elicited a systemic allergic reaction that was greatly reduced by sulfapyridine (1 and 10 μg/kg; intraperitoneal injection) [4].
In vivo, sulfapyridine is the major active metabolite of the prodrug sulfasalazine. After oral administration of sulfasalazine, the azo bond is cleaved by intestinal bacteria, releasing sulfapyridine and 5-aminosalicylic acid (5-ASA). Sulfapyridine is absorbed into the systemic circulation and exerts its antibacterial and anti-inflammatory effects. It is used clinically for the treatment of several dermatological conditions, including dermatitis herpetiformis. It also has anti-rheumatic activity and is used in the treatment of rheumatoid arthritis. The compound has been shown to inhibit mast cell-mediated immediate-type allergic reactions in vivo. Sulfapyridine is considered a xenobiotic, environmental pollutant, and drug allergen.

In vitro enzyme/receptor binding assays for sulfapyridine typically involve evaluating its inhibitory activity against purified dihydropteroate synthetase (DHPS). The enzyme is incubated with varying concentrations of sulfapyridine and a fixed concentration of para-aminobenzoic acid (PABA), along with the co-substrate 6-hydroxymethyl-7,8-dihydropterin pyrophosphate (DHPPP). The reaction is monitored by measuring the formation of dihydropteroate, and the IC50 value is determined as the concentration of sulfapyridine required to inhibit enzyme activity by 50%. In addition to enzyme assays, sulfapyridine's anti-inflammatory activity can be evaluated in vitro by measuring its ability to inhibit the production of pro-inflammatory cytokines such as IL-8, CXCL1, and MCP-1 in cultured synovial cells.

For in vitro cell-based assays, sulfapyridine is dissolved in DMSO and applied to cultured cells at concentrations ranging from 1 µM to 100 µM. It is used to study its effects on cytokine production in synovial cells from rheumatoid arthritis patients. Cells are treated with sulfapyridine for specific periods, and the levels of IL-8, CXCL1, and MCP-1 in the culture supernatant are measured using ELISA. The compound's ability to inhibit mast cell-mediated immediate-type allergic reactions can also be evaluated in vitro using mast cell models. Effects on cell viability and proliferation are assessed using standard assays such as MTT or trypan blue exclusion.

In vivo animal studies for sulfapyridine are typically conducted in rodent models to evaluate its anti-inflammatory and immunosuppressive effects. The compound is administered orally or intraperitoneally at doses ranging from 10-100 mg/kg. Efficacy is evaluated by measuring the inhibition of inflammatory responses, such as mast cell-mediated immediate-type allergic reactions. In models of rheumatoid arthritis, sulfapyridine is used to study its effects on synovial inflammation and joint destruction. The compound's ability to modulate immune responses and cytokine production is assessed by measuring levels of inflammatory markers in serum and tissues.

Absorption, Distribution and Excretion
Approximately 60-80% of the metabolism/metabolites are metabolized by the liver. Known metabolites of sulfapyridine include sulfapyridine N-acetyl. Biological Half-Life: 6-14 hours.
Sulfapyridine has a molecular weight of 249.29 g/mol and a molecular formula of C11H11N3O2S. It is practically insoluble in water (< 0.1 mg/mL). The compound is typically stored as a powder at -20°C for long-term stability. Sulfapyridine is the major metabolite of sulfasalazine and is used as an analytical standard in research and analytical applications. It belongs to the pyridine, sulfonamide, substituted aniline, and sulfonamide antibiotic classes. Sulfapyridine is also classified as a xenobiotic, environmental pollutant, and drug allergen.

Protein Binding
Approximately 50% is bound to plasma proteins.
Sulfapyridine is considered to have a manageable toxicity profile, consistent with other sulfonamide antibiotics. Common adverse effects include hypersensitivity reactions, such as skin rashes and photosensitivity. Hematological toxicities, including agranulocytosis and hemolytic anemia, can occur, particularly in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Renal toxicity, such as crystalluria, is a risk due to the precipitation of sulfonamide metabolites in the urine. Gastrointestinal disturbances, including nausea and vomiting, are also reported. Sulfapyridine is classified as a drug allergen. Its use in treating dermatitis herpetiformis is associated with dose-related side effects, and monitoring of blood counts and renal function is recommended during therapy.

[1]. Effects of salazosulfapyridine on the profile of cell surface proteins, revealed by biotinylation of cell surface proteins and 2-dimentional electrophoresis. Biochim Biophys Acta Proteins Proteom. 2019 Jan;1867(1):47-56.

[2]. In vitro susceptibility of diarrhoea producing gram negative enteric bacteria to sulfasalazine, 5-aminosalicylic acid, sulfapyridine and four quinolones. Brief report. APMIS. 1988 Jun;96(6):568-70.

[3]. Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs. Antimicrob Agents Chemother. 1995 Aug;39(8):1756-63.

[4]. Inhibitory effect of mast cell-mediated immediate-type allergic reactions by sulfapyridine. Immunopharmacol Immunotoxicol. 2000 May;22(2):253-66.

Sulfapyridine is an odorless or nearly odorless white or pale yellow crystalline powder with a slightly bitter taste. Its aqueous solution is neutral. (NTP, 1992)
Sulfapyridine is a sulfonamide compound consisting of a pyridine ring with a 4-aminobenzenesulfonamide group attached at the 2-position. It is used as an anti-infective agent, dermatological drug, xenobiotic, environmental pollutant, and drug allergen. It belongs to the pyridine, sulfonamide, substituted aniline, and sulfonamide antibiotic classes. Its function is related to sulfonamide compounds.
It has antibacterial activity but may be toxic; it was once used to treat certain skin diseases. It is now discontinued.
Sulfapyridine is a short-acting sulfonamide antibiotic, a byproduct of the nonsteroidal anti-inflammatory drug sulfasalazine. Its production and use were discontinued in 1990.
An antibacterial drug, possibly toxic, used to treat certain skin diseases.
See also: Sulfapyridine sodium (in salt form). Indications For the treatment of dermatitis herpetiformis, benign mucosal pemphigoid, and pyoderma gangrenosa. Mechanism of Action Sulfapyridine is a competitive inhibitor of bacterial dihydropteranoic acid synthase. Inhibition of this enzyme is crucial for these organisms to synthesize folic acid by processing the substrate para-aminobenzoic acid (PABA). The activity of dihydropteranoic acid synthase is essential for folic acid synthesis, which is necessary for the synthesis of nucleic acids such as DNA or RNA by cells. Therefore, if DNA molecules cannot be synthesized, cells cannot divide. Pharmacodynamics Sulfapyridine is a sulfonamide antibiotic. Sulfonamides are synthetic antibacterial antibiotics with broad-spectrum antibacterial activity against most Gram-positive bacteria and many Gram-negative bacteria. However, many strains of the same bacterial species may develop resistance. Sulfonamides inhibit bacterial growth by competitively inhibiting para-aminobenzoic acid in the folic acid metabolic cycle. Bacteria exhibit similar sensitivity to various sulfonamides; resistance to one sulfonamide implies resistance to all sulfonamides. Most sulfonamides are well absorbed orally. However, parenteral administration is challenging due to the strong alkalinity and tissue irritation of soluble sulfonamide salts. Sulfonamides are widely distributed in all tissues. High concentrations can be reached in pleural fluid, peritoneal fluid, synovial fluid, and ocular fluid. Although these drugs are no longer used to treat meningitis, high concentrations remain in the cerebrospinal fluid of patients with meningeal infections. Pus can inhibit their antibacterial activity.
Sulfapyridine is a sulfonamide antibiotic and the major active metabolite of the prodrug sulfasalazine. It acts as a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase (DHPS), with an IC50 of 0.18 µM. Sulfapyridine has antibacterial, anti-inflammatory, and anti-rheumatic activities. It is primarily indicated for the treatment of dermatitis herpetiformis and other dermatological conditions. In addition to its antimicrobial properties, it has anti-inflammatory effects, making it useful in treating autoimmune conditions. Sulfapyridine inhibits the production of IL-8, CXCL1, and MCP-1 in synovial cells of rheumatoid arthritis patients. It is classified as a pyridine, sulfonamide, substituted aniline, and sulfonamide antibiotic.

C11H11N3O2S

249.288

249.057

144-83-2

Sulfapyridine-d4;1189863-86-2

5336

White to off-white solid powder

1.4±0.1 g/cm3

473.5±51.0 °C at 760 mmHg

191-193°C

240.2±30.4 °C

0.0±1.2 mmHg at 25°C

1.674

0.03

2

5

3

17

331

0

GECHUMIMRBOMGK-UHFFFAOYSA-N

InChI=1S/C11H11N3O2S/c12-9-4-6-10(7-5-9)17(15,16)14-11-3-1-2-8-13-11/h1-8H,12H2,(H,13,14)

4-amino-N-pyridin-2-ylbenzenesulfonamide

A-499; A499; A 499

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~60 mg/mL (~240.68 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 3 mg/mL (12.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 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.

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Solubility in Formulation 2: ≥ 3 mg/mL (12.03 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
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.

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Solubility in Formulation 3: ≥ 3 mg/mL (12.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 30.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)