Aminosalicylic acid targets the enzyme dihydropteroate synthase in Mycobacterium tuberculosis. By structurally mimicking PABA, it acts as a competitive inhibitor of this enzyme, blocking the incorporation of PABA into dihydropteroic acid, a precursor of folic acid. This inhibition disrupts folate synthesis, which is essential for bacterial DNA synthesis and cell division. Aminosalicylic acid is bacteriostatic against actively growing M. tuberculosis.

In vitro, Aminosalicylic acid has been shown to inhibit the growth of Mycobacterium tuberculosis in a concentration-dependent manner. It is bacteriostatic, meaning it inhibits bacterial growth rather than killing the bacteria directly. The minimum inhibitory concentration (MIC) for susceptible strains of M. tuberculosis is typically in the range of 1-8 µg/mL. Aminosalicylic acid is also active against some other mycobacterial species. In vitro studies have also investigated its effects on folate synthesis in bacterial cells.

In vivo, Aminosalicylic acid is used clinically for the treatment of tuberculosis, particularly in patients with drug-resistant disease or those who cannot tolerate first-line agents. It is administered orally and is typically used in combination with other antitubercular drugs such as isoniazid, rifampin, and streptomycin. Aminosalicylic acid has been shown to be effective in reducing bacterial load and improving clinical outcomes in patients with tuberculosis.

In vitro susceptibility testing for Aminosalicylic acid is typically performed using broth microdilution or agar dilution methods. The compound is dissolved in appropriate solvents and diluted in culture medium. The MIC is determined as the lowest concentration that inhibits visible growth of M. tuberculosis after incubation at 37°C for 2-3 weeks. The compound's activity against M. tuberculosis is assessed in comparison to standard strains and quality control organisms.

In vitro cell-based studies with Aminosalicylic acid typically involve cultured macrophages infected with M. tuberculosis. The compound is added to the culture medium at various concentrations, and its ability to inhibit intracellular bacterial growth is assessed by colony counting or by measuring bacterial metabolic activity. The effect of Aminosalicylic acid on macrophage function and cytokine production can also be evaluated.

In vivo animal studies with Aminosalicylic acid have been conducted in mouse and guinea pig models of tuberculosis. Animals are infected with M. tuberculosis and then treated with Aminosalicylic acid alone or in combination with other antitubercular drugs. The efficacy of treatment is assessed by measuring bacterial load in the lungs and spleen, by monitoring survival, and by histopathological examination of tissues. Pharmacokinetic studies are also performed to evaluate the absorption and distribution of the compound.

Absorption, Distribution and Excretion
Bioavailability studies of aminosalicylic acid and its salts were conducted in 12 subjects. Colorimetric assays showed peak plasma concentrations of the sodium, potassium, calcium, and para-aminosalicylic acid salts at 0.5, 0.75, 1.5, and 3 hours, respectively. Urinary excretion data indicated that absorption was essentially complete, although absorption rates varied. Aminosalicylic acid is readily absorbed from the gastrointestinal tract. Following a single oral dose of 4 grams of free acid, plasma concentrations reached approximately 75 μg/mL within 1.5 to 2 hours. Sodium salts were absorbed more rapidly. The drug appears to be distributed throughout the body fluids, reaching higher concentrations in pleural fluid and caseous tissue. However, lower concentrations were observed in cerebrospinal fluid, likely due to active efflux. Over 80% of the drug was excreted in the urine; of this, over 50% was excreted as acetylated compounds. The remainder consisted primarily of free acid. For more complete data on the absorption, distribution, and excretion of para-aminosalicylic acid (8 metabolites), please visit the HSDB record page.

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Metabolism/Metabolites
Hepatic metabolism.
Acetylation is a major pathway for the inactivation of many drugs, such as para-aminosalicylic acid. The enzyme that catalyzes these reactions, acetyl-CoA:N-acetyltransferase (EC 2.3.1.5), is located in the hepatocyte lysate.
After oral administration, para-aminosalicylic acid is rapidly absorbed and excreted in the urine as unaltered para-aminosalicylic acid and acetyl. Glucuronide, glycyl, and glutamyl conjugates.
In humans, it produces 5-amino-2-carboxyphenyl-β-D-glucuronide. In Pseudomonas, it produces 4-aminocatechol. In humans, it produces 4-aminosalicylglutamine and 4-aminosalicylglycine. /Table/
Blood was collected from tuberculosis patients before, during, and after treatment with five different drug combinations: isoniazid, thiazolidinedone, para-aminosalicylic acid, and streptomycin, for culture. Methods for detecting DNA damage included chromosomal aberrations and sister chromatid exchange (SCE). A total of 179 subjects were analyzed. These drugs showed synergistic, additive, and antagonistic effects when used in combination, but none were found to cause chromosome breakage when used alone. Four drug combinations—isoniazid with thiazolidinedone, isoniazid with para-aminosalicylic acid, isoniazid with thiazolidinedone and streptomycin, and isoniazid with para-aminosalicylic acid and streptomycin—significantly increased the incidence of chromosomal aberrations, while isoniazid with streptomycin did not induce chromosomal aberrations. In fact, streptomycin appeared to reduce the incidence of chromosomal aberrations. Only two patients showed an increased incidence of sister chromatid exchange (SCE): one treated with isoniazid with thiazolidinedone and the other treated with isoniazid with para-aminosalicylic acid. The incidence of chromosomal aberrations decreased after drug discontinuation; although slightly higher than the control group, the difference was not statistically significant. Recovery from chromosomal aberrations may be due to the clearance of damaged cells or DNA repair in lymphocytes. Although drug-induced abnormalities do not persist after discontinuation, caution should still be exercised when using this combination of chromosomal-damaging drugs, as the possibility of chromosomal damage occurring during germ cell meiosis during treatment cannot be ruled out, and such damage may be inherited by the next generation. For more complete metabolite/metabolite data on para-aminosalicylic acid (9 metabolites), please visit the HSDB record page. The half-life of this drug is approximately 1 hour, and plasma concentrations are negligible within 4 to 5 hours after a single dose.
Aminosalicylic acid is a well-characterized drug with established pharmacokinetic properties. Following oral administration, it is rapidly absorbed from the gastrointestinal tract. It is extensively metabolized in the liver, primarily by acetylation. The acetylated metabolite is inactive. Aminosalicylic acid is excreted in the urine, primarily as metabolites. The half-life of Aminosalicylic acid is approximately 1-2 hours. Food intake can affect the absorption of the drug.

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
Limited information suggests that low concentrations of aminosalicylic acid in breast milk are not expected to cause any adverse effects on breastfed infants, especially those older than 2 months. If this medication is used during lactation, exclusively breastfed infants should be monitored for rare occurrences such as jaundice, gastrointestinal disturbances, hypokalemia, thrombocytopenia, hemolysis, and hypokalemia.
◉ Effects on Breastfed Infants
Aminosalicylic acid was used as part of a multidrug regimen to treat two pregnant women with multidrug-resistant tuberculosis throughout pregnancy and postpartum. Both of their infants were breastfed (the extent and duration of breastfeeding were not specified). Both children were developmentally normal at 1.8 and 4.6 years of age, respectively. One child showed mild language delay at 1.8 years, while the other experienced growth retardation, possibly due to tuberculosis infection after birth.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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Protein binding
50-60%

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Interactions
...para-aminosalicylic acid.../Inhibition of chloramphenicol metabolism/
Pentobarbital/SRP: Central nervous system depression/Enhanced in mice after pretreatment with para-aminosalicylic acid. INCR/SRP: Central nervous system depression/Appears to be due to the release of pentobarbital from serum protein binding, leading to increased brain concentrations...
Additive and synergistic effects with streptomycin and isoniazid.
Probenecid reduces renal excretion of this drug.
For more (complete) data on interactions of para-aminosalicylic acid (19 in total), please visit the HSDB record page.
Aminosalicylic acid is a clinically approved drug with a well-established safety profile. The most common adverse effects are gastrointestinal, including nausea, vomiting, abdominal pain, and diarrhea. Hypersensitivity reactions, including fever, rash, and hepatitis, can occur. Hematological effects, including anemia, leukopenia, and thrombocytopenia, have been reported. Thyroid enlargement and goiter can occur with long-term use. Patients should be monitored for hepatotoxicity and renal function during treatment.

4-Aminosalicylic acid is an aminobenzoic acid formed by substituting an amino group at the 4-position of salicylic acid. It is an anti-tuberculosis drug. It belongs to the aminobenzoic acid class of compounds and is also a phenolic compound. Its function is related to that of salicylic acid. It is the conjugate acid of 4-aminosalicylic acid (1-). It is an anti-tuberculosis drug, often used in combination with isoniazid. The sodium salt of this drug is better tolerated than the free acid. Aminosalicylic acid is a para-aminobenzoic acid (PABA) analog with anti-tuberculosis activity. Aminosalicylic acid inhibits the growth and reproduction of Mycobacterium tuberculosis by competing with para-aminobenzoic acid (PABA) for folic acid synthase, ultimately leading to cell death and exerting its antibacterial effect. Sodium aminosalicylate is the sodium salt form of aminosalicylic acid and is a para-aminobenzoic acid (PABA) analog with anti-tuberculosis activity. Sodium aminosalicylate exerts its antibacterial effect by competing with para-aminobenzoic acid (PABA) for folate synthase, thereby inhibiting the growth and reproduction of Mycobacterium tuberculosis, ultimately leading to cell death. Sodium aminosalicylate is an anti-tuberculosis drug, often used in combination with isoniazid. The sodium salt of this drug is better tolerated than the free acid. Drug Indications For the treatment of tuberculosis. When an effective treatment regimen cannot be established due to drug resistance or tolerance (see Section 4.4), Granupas is indicated for combination therapy of multidrug-resistant tuberculosis in adults and children 28 days and older. Official guidelines for the rational use of antimicrobial drugs should be consulted. Mechanism of Action The antibacterial effect of aminosalicylate against Mycobacterium tuberculosis is mainly achieved through two mechanisms. First, aminosalicylate inhibits folate synthesis (without synergistic effect with antifolate compounds). The binding of para-aminobenzoic acid to pterin synthase is the first step in folate synthesis. Aminosalicylic acid has a higher affinity for pterin synthase than para-aminobenzoic acid, effectively inhibiting folic acid synthesis. Because bacteria cannot utilize exogenous folic acid, cell growth and reproduction slow down. Secondly, aminosalicylic acid may inhibit the synthesis of mycotoxin, a cell wall component, thereby reducing iron absorption by Mycobacterium tuberculosis. The antibacterial activity of aminosalicylic acid is highly specific, affecting microorganisms other than Mycobacterium tuberculosis. Most non-tuberculous mycobacteria are not inhibited by this drug. Aminosalicylic acid is a structural analog of para-aminobenzoic acid, and its mechanism of action is very similar to that of sulfonamides. Since sulfonamides are ineffective against Mycobacterium tuberculosis, and aminosalicylic acid is also ineffective against bacteria sensitive to sulfonamides, the enzymes responsible for folic acid biosynthesis in various microorganisms may have a strong ability to distinguish between various analogs and true metabolites.

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Therapeutic Uses
Anti-tuberculosis drug
Experimental Use: Lipid-lowering drug. 6 grams, taken for 4 weeks. Results showed that it can reduce elevated serum triglyceride and cholesterol levels. When used alone, it can sometimes successfully control tuberculosis…but resistance can develop, and toxicity limits the dosage. Therefore, para-aminosalicylic acid is almost always used in combination with one or two other anti-tuberculosis drugs. …para-aminosalicylic acid can enhance the efficacy of other drugs and delay the onset of resistance. Aminosalicylic acid…has a potent lipid-lowering effect, reducing cholesterol and triglyceride levels. However, it is poorly tolerated due to gastrointestinal reactions. For more complete data on the therapeutic uses of para-aminosalicylic acid (15 in total), please visit the HSDB record page.

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Drug Warnings
Under no circumstances should the solution be used if its color is darker than freshly prepared solution. …Calcium, potassium, and sodium salt solutions should be prepared within 24 hours of administration.
For certain disorders that appear to be ethnically specific (such as glucose-6-phosphate dehydrogenase deficiency in erythrocytes), different drugs can cause hemolysis. Among the most notable are nitrofurantoin, aminosalicylic acid…
In patients with impaired renal function or other disorders affecting plasma concentration control, this drug can cause hypercalcemia. It can also cause urinary tract stones. /CA SALT/
The most common adverse reactions to aminosalicylic acid or its salts are gastrointestinal disturbances, including nausea, vomiting, abdominal pain, diarrhea, and anorexia. Rarely, aminosalicylic acid causes peptic ulcers and gastrointestinal bleeding. Some patients can alleviate gastrointestinal adverse reactions by taking aminosalicylic acid with food; however, symptoms may be severe enough to require discontinuation of the drug. Occasionally, patients taking aminosalicylic acid or its salts may also experience malabsorption of vitamin B12, folic acid, iron, and lipids, possibly due to increased intestinal motility. The manufacturer notes that maintenance therapy with vitamin B12 should be considered for patients taking aminosalicylic acid for more than one month. For more complete data on p-aminosalicylic acid (12 in total), please visit the HSDB records page.

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Pharmacodynamics
Aminosalicylic acid is an antimycobacterial drug, often used in combination with other antituberculosis drugs (most commonly isoniazid) to treat various types of active tuberculosis caused by susceptible strains of Mycobacterium tuberculosis. Two key considerations in the clinical pharmacology of aminosalicylic acid are: the rapid production of toxic, inactive metabolites under acidic conditions, and the serum half-life of the free drug of only 1 hour. Aminosalicylic acid has an inhibitory effect on Mycobacterium tuberculosis (inhibiting bacterial growth without killing the bacteria). It also inhibits the development of bacterial resistance to streptomycin and isoniazid.
Aminosalicylic acid is a clinically approved antibiotic used for the treatment of tuberculosis, particularly multidrug-resistant tuberculosis. It is classified as a second-line antitubercular agent and is used in combination with other drugs to prevent the development of resistance. Aminosalicylic acid is available in various formulations, including tablets, capsules, and granules. The compound has been in clinical use for over 70 years and remains an important component of tuberculosis treatment regimens in cases of drug resistance. It is available under various brand names.

C7H7NO3

153.1354

153.042

65-49-6

Sodium 4-aminosalicylate dihydrate;6018-19-5;4-Aminosalicylic acid hemicalcium;133-15-3

4649

MINUTE CRYSTALS FROM ALC
WHITE, OR NEARLY WHITE, BULKY POWDER
NEEDLES, PLATES FROM ALC-ETHER
A reddish-brown crystalline powder is obtained on recrystallization from ethanol-ether.

1.5±0.1 g/cm3

380.8±32.0 °C at 760 mmHg

135-145 °C(lit.)

184.1±25.1 °C

0.0±0.9 mmHg at 25°C

1.691

1.14

3

4

1

11

160

0

O([H])C1C([H])=C(C([H])=C([H])C=1C(=O)O[H])N([H])[H]

WUBBRNOQWQTFEX-UHFFFAOYSA-N

InChI=1S/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11)

4-amino-2-hydroxybenzoic acid

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 : ~100 mg/mL (~653.00 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.32 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 25.0 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: ≥ 2.5 mg/mL (16.32 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 25.0 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: ≥ 2.5 mg/mL (16.32 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 25.0 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.)