You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:19 UTC
HMDB IDHMDB14378
Secondary Accession NumbersNone
Metabolite Identification
Common NameAminosalicylic Acid
DescriptionAminosalicylic Acid is only found in individuals that have used or taken this drug. It is an antitubercular agent often administered in association with isoniazid. The sodium salt of the drug is better tolerated than the free acid. [PubChem]There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against Mycobacterium tuberculosis. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slows. Secondly, aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis.
Structure
Thumb
Synonyms
ValueSource
2-HYDROXY-4-aminobenzoIC ACIDChEBI
4-AminosalicylateChEBI
P-Aminosalicylic acidChEBI
Para-amino salicylic acidChEBI
PASChEBI
PaserChEBI
2-HYDROXY-4-aminobenzoateGenerator
AminosalicylateGenerator
4-Aminosalicylic acidGenerator
P-AminosalicylateGenerator
Para-amino salicylateGenerator
4-ASAHMDB
amino-PASHMDB
Aminosalicylate sodiumHMDB
APASHMDB
Para-aminosalicylic acidHMDB
PASKHMDB
Chemical FormulaC7H7NO3
Average Molecular Weight153.1354
Monoisotopic Molecular Weight153.042593095
IUPAC Name4-amino-2-hydroxybenzoic acid
Traditional Nameaminosalicylic acid
CAS Registry Number65-49-6
SMILES
NC1=CC(O)=C(C=C1)C(O)=O
InChI Identifier
InChI=1S/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11)
InChI KeyInChIKey=WUBBRNOQWQTFEX-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aminosalicylic acids. These are salicylic acids carrying an amino group on the benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzoic acids and derivatives
Direct ParentAminosalicylic acids
Alternative Parents
Substituents
  • Aminosalicylic acid
  • Salicylic acid
  • Aminobenzoic acid or derivatives
  • Aminobenzoic acid
  • Benzoic acid
  • Substituted aniline
  • Benzoyl
  • Aminophenol
  • Phenol
  • Aniline
  • Primary aromatic amine
  • Vinylogous acid
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antitubercular Agents
  • Antituberculosis Agents
Application
  • Pharmaceutical
Cellular locations
  • Cytoplasm
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point150.5 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility1.18e+01 g/LNot Available
LogP1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility11.8 mg/mLALOGPS
logP0.62ALOGPS
logP0.83ChemAxon
logS-1.1ALOGPS
pKa (Strongest Acidic)3.68ChemAxon
pKa (Strongest Basic)2.19ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area83.55 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity40 m3·mol-1ChemAxon
Polarizability14.29 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00233
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00233
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00233
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4488
KEGG Compound IDC02518
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkAminosalicylic_acid
NuGOwiki LinkHMDB14378
Metagene LinkHMDB14378
METLIN IDNot Available
PubChem Compound4649
PDB IDBHA
ChEBI ID27565
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. ARTIS RD, JOHNSON PK, FREE AH: A simplified test for the detection of paraaminosalicylic acid and acetylsalicylic acid metabolites in urine. Am Rev Respir Dis. 1961 Sep;84:435-9. [13684569 ]
  2. JUHASZ P, GALAMBOS G: [A simple paper-indicator method for the demonstration of paraaminosalicylic acid (PAS) in urine]. Tuberkulozis. 1961 Jun;14:186-7. [13790963 ]
  3. Iyawoo K: Tuberculosis in Malaysia: problems and prospect of treatment and control. Tuberculosis (Edinb). 2004;84(1-2):4-7. [14670340 ]
  4. Controlled trial of short-course regimens of chemotherapy in the ambulatory treatment of spinal tuberculosis. Results at three years of a study in Korea. Twelfth report of the Medical Research Council Working Party on Tuberculosis of the Spine. J Bone Joint Surg Br. 1993 Mar;75(2):240-8. [8444944 ]
  5. Tiitinen H, Mattila MJ: Modification of the serum isoniazid levels by different preparations of paraaminosalicylic acid. Arzneimittelforschung. 1968 May;18(5):623-5. [5755895 ]
  6. Ojo OA, Onifade A, Akande EO, Bannerman RH: The pattern of female genital tuberculosis in Ibadan. Isr J Med Sci. 1971 Feb;7(2):280-7. [5560983 ]
  7. Shah A, Panjabi C, Maurya V, Khanna P: Multidrug resistant miliary tuberculosis and Pott's disease in an immunocompetent patient. Saudi Med J. 2004 Oct;25(10):1468-70. [15494824 ]
  8. NAITO M: [Combined therapy of massive doses of isoniazid, pyrazinamide, and sulfisoxazole for patients with pulmonary tuberculosis resistant to streptomycin, paraaminosalicylic acid, and isoniazid]. Kyoto Daigaku Kekkaku Kenkyusho Kiyo. 1961 Mar;9:136-41. [14478036 ]
  9. KENDIG EL Jr, HUDGENS RO: The effect of rubeola on tuberculosis under antimicrobial therapy. II. Tuberculous meningitis treated with isoniazid, streptomycin and paraaminosalicylic acid. Pediatrics. 1959 Oct;24:619-22. [14408481 ]
  10. Joshi JV, Joshi UM, Sankolli GM, Gupta K, Rao AP, Hazari K, Sheth UK, Saxena BN: A study of interaction of a low-dose combination oral contraceptive with anti-tubercular drugs. Contraception. 1980 Jun;21(6):617-29. [7428368 ]
  11. MITROIU O, POPA M, NEGREANU W, BILCU M, POPPER M, KAUFMANN S, NICULESCU V, VANCOV Z: [The differential diagnosis of jaundices appearing during treatment with paraaminosalicylic acid (PAS) by means of serum aldolase determination]. Stud Cercet Inframicrobiol. 1960;11:125-31. [14423031 ]
  12. MILLER FF, GREEN RA: Loeffler's syndrome due to paraaminosalicylic acid. Dis Chest. 1962 Jul;42:100-3. [14473996 ]
  13. Miroshnichenko II, Sokolova GB, Mokhireva LV: [Clinical pharmacokinetics of para-aminosalicylic acid tablets]. Antibiot Khimioter. 2009;54(1-2):20-4. [19499713 ]
  14. SCHMITTOVA M, ENGELBERTH O, SRAMKOVA J: [Effect of aminopyrine, paraaminobenzoic acid and paraaminosalicylic acid on experimental carditis in mice]. Cas Lek Cesk. 1959 Oct 30;98:1365-9. [14443158 ]
  15. Wong SC, Ali MA: Hemoglobin E diseases: hematological, analytical, and biosynthetic studies in homozygotes and double heterozygotes for alpha-thalassemia. Am J Hematol. 1982 Aug;13(1):15-21. [7137163 ]
  16. Costello HD, Caras GJ, Snider DE Jr: Drug resistance among previously treated tuberculosis patients, a brief report. Am Rev Respir Dis. 1980 Feb;121(2):313-6. [6767427 ]
  17. LEHMANN J: TWENTY YEARS AFTERWARD HISTORICAL NOTES ON THE DISCOVERY OF THE ANTITUBERCULOSIS EFFECT OF PARAAMINOSALICYLIC ACID (PAS) AND THE FIRST CLINICAL TRIALS. Am Rev Respir Dis. 1964 Dec;90:953-6. [14233801 ]
  18. Vachova-Fribova M, Elis J: [Effect of theophylline and isoprenaline on N-acetylation activity in the rat liver]. Farmakol Toksikol. 1978 Mar-Apr;41(2):191-3. [658363 ]
  19. Bader G: [Electron microscopic studies on pathological liver regeneration under the influence of thioacetamide, paraaminosalicylic acid and barbiturate]. Acta Hepatosplenol. 1969 May-Jun;16(3):160-73. [5799611 ]

Enzymes

General function:
Involved in phospholipase A2 activity
Specific function:
PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Has a preference for arachidonic-containing phospholipids.
Gene Name:
PLA2G2E
Uniprot ID:
Q9NZK7
Molecular weight:
15988.525
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
General function:
Involved in peroxidase activity
Specific function:
Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity.
Gene Name:
MPO
Uniprot ID:
P05164
Molecular weight:
83867.71
References
  1. von Ritter C, Grisham MB, Granger DN: Sulfasalazine metabolites and dapsone attenuate formyl-methionyl-leucyl-phenylalanine-induced mucosal injury in rat ileum. Gastroenterology. 1989 Mar;96(3):811-6. [2563347 ]
  2. Gorgulu S, Yagci G, Kaymakcioglu N, Ozkara M, Kurt B, Ozcan A, Kaya O, Sadir S, Tufan T: Hyperbaric oxygen enhances the efficiency of 5-aminosalicylic acid in acetic acid-induced colitis in rats. Dig Dis Sci. 2006 Mar;51(3):480-7. [16614956 ]
General function:
Involved in metal ion binding
Specific function:
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:
ALOX5
Uniprot ID:
P09917
Molecular weight:
77982.595
References
  1. Nielsen OH, Bukhave K, Elmgreen J, Ahnfelt-Ronne I: Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid. Dig Dis Sci. 1987 Jun;32(6):577-82. [2882965 ]
  2. Allgayer H, Eisenburg J, Paumgartner G: Soybean lipoxygenase inhibition: studies with the sulphasalazine metabolites N-acetylaminosalicylic acid, 5-aminosalicylic acid and sulphapyridine. Eur J Clin Pharmacol. 1984;26(4):449-51. [6428914 ]
  3. Sircar JC, Schwender CF, Carethers ME: Inhibition of soybean lipoxygenase by sulfasalazine and 5-aminosalicylic acid: a possible mode of action in ulcerative colitis. Biochem Pharmacol. 1983 Jan 1;32(1):170-2. [6131674 ]
General function:
Involved in peroxidase activity
Specific function:
Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.
Gene Name:
PTGS2
Uniprot ID:
P35354
Molecular weight:
68995.625
References
  1. Mifflin RC, Saada JI, Di Mari JF, Valentich JD, Adegboyega PA, Powell DW: Aspirin-mediated COX-2 transcript stabilization via sustained p38 activation in human intestinal myofibroblasts. Mol Pharmacol. 2004 Feb;65(2):470-8. [14742690 ]
  2. Generini S, Fiori G, Matucci Cerinic M: Therapy of spondylarthropathy in inflammatory bowel disease. Clin Exp Rheumatol. 2002 Nov-Dec;20(6 Suppl 28):S88-94. [12463455 ]
  3. Distrutti E, Sediari L, Mencarelli A, Renga B, Orlandi S, Russo G, Caliendo G, Santagada V, Cirino G, Wallace JL, Fiorucci S: 5-Amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester (ATB-429), a hydrogen sulfide-releasing derivative of mesalamine, exerts antinociceptive effects in a model of postinflammatory hypersensitivity. J Pharmacol Exp Ther. 2006 Oct;319(1):447-58. Epub 2006 Jul 19. [16855178 ]
  4. Cipolla G, Crema F, Sacco S, Moro E, de Ponti F, Frigo G: Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current perspectives. Pharmacol Res. 2002 Jul;46(1):1-6. [12208114 ]
  5. Pruzanski W, Stefanski E, Vadas P, Ramamurthy NS: Inhibition of extracellular release of proinflammatory secretory phospholipase A2 (sPLA2) by sulfasalazine: a novel mechanism of anti-inflammatory activity. Biochem Pharmacol. 1997 Jun 15;53(12):1901-7. [9256165 ]
General function:
Involved in protein kinase activity
Specific function:
Acts as part of the IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF- kappa-B complex and ultimately the degradation of the inhibitor. As part of the non-canonical pathway of NF-kappa-B activation, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. Also phosphorylates NCOA3. Phosphorylates 'Ser-10' of histone H3 at NF- kappa-B-regulated promoters during inflammatory responses triggered by cytokines
Gene Name:
CHUK
Uniprot ID:
O15111
Molecular weight:
84652.9
References
  1. Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K: Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol. 2000 Dec;95(12):3452-7. [11151876 ]
  2. Allgayer H: Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:10-4. [12950415 ]
  3. Weber CK, Liptay S, Wirth T, Adler G, Schmid RM: Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology. 2000 Nov;119(5):1209-18. [11054378 ]