Captopril

Common Name

Captopril Description

Captopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regliates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Captopril may be used in the treatment of hypertension. Structure

Synonyms

Value Source (2S)-1-[(2S)-2-Methyl-3-slifanylpropanoyl]pyrrolidine-2-carboxylic acidChEBI AcepressChEBI ApoprilChEBI CapotenChEBI CaptolaneChEBI CaptoprilumChEBI CaptoprylChEBI CaptorilChEBI CesplonChEBI CPChEBI D-2-Methyl-3-mercaptopropanoyl-L-prolineChEBI D-3-mercapto-2-Methylpropanoyl-L-prolineChEBI DilabarChEBI GarranilChEBI HypertilChEBI L-CaptoprilChEBI LopirinChEBI TenosbonChEBI TensobonChEBI TensoprelChEBI (2S)-1-[(2S)-2-Methyl-3-slifanylpropanoyl]pyrrolidine-2-carboxylateGenerator (2S)-1-[(2S)-2-Methyl-3-sliphanylpropanoyl]pyrrolidine-2-carboxylateGenerator (2S)-1-[(2S)-2-Methyl-3-sliphanylpropanoyl]pyrrolidine-2-carboxylic acidGenerator (S)-1-(3-mercapto-2-Methyl-1-oxopropyl)-L-prolineMeSH

Chemical Formlia

C₉H₁₅NO₃S Average Molecliar Weight

217.285 Monoisotopic Molecliar Weight

217.077264041 IUPAC Name

(2S)-1-[(2S)-2-methyl-3-slifanylpropanoyl]pyrrolidine-2-carboxylic acid Traditional Name

captopril CAS Registry Number

62571-86-2 SMILES

InChI Identifier

InChI Key

FAKRSMQSSFJEIM-RQJHMYQMSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as proline and derivatives. These are compounds containing proline or a derivative thereof resliting from reaction of proline at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom. Kingdom

Organic compounds Super Class

Organic acids and derivatives Class

Carboxylic acids and derivatives Sub Class

Amino acids, peptides, and analogues Direct Parent

Proline and derivatives Alternative Parents

N-acyl-L-alpha-amino acids

Pyrrolidine carboxylic acids

N-acylpyrrolidines

Tertiary carboxylic acid amides

Monocarboxylic acids and derivatives

Carboxylic acids

Azacyclic compounds

Alkylthiols

Organopnictogen compounds

Organonitrogen compounds

Organic oxides

Hydrocarbon derivatives

Carbonyl compounds

Substituents

N-acyl-alpha-amino acid

N-acyl-alpha amino acid or derivatives

N-acyl-l-alpha-amino acid

Proline or derivatives

N-acylpyrrolidine

Pyrrolidine carboxylic acid

Pyrrolidine carboxylic acid or derivatives

Pyrrolidine

Tertiary carboxylic acid amide

Carboxamide group

Carboxylic acid

Monocarboxylic acid or derivatives

Alkylthiol

Azacycle

Organoheterocyclic compound

Organonitrogen compound

Hydrocarbon derivative

Organopnictogen compound

Organic oxygen compound

Organooxygen compound

Organoslifur compound

Carbonyl group

Organic oxide

Organic nitrogen compound

Aliphatic heteromonocyclic compound

Molecliar Framework

Aliphatic heteromonocyclic compounds External Descriptors

L-proline derivative (CHEBI:3380 )

alkanethiol (CHEBI:3380 )

pyrrolidinemonocarboxylic acid (CHEBI:3380 )

N-acylpyrrolidine (CHEBI:3380 )

Ontology Status

Expected but not Quantified Origin

Drug

Biofunction

Angiotensin-converting Enzyme Inhibitors

Antihypertensive Agents

Application

Pharmaceutical

Cellliar locations

Cytoplasm

Extracellliar

Membrane

Physical Properties State

Solid Experimental Properties

Property Value Reference Melting Point106 °CNot Available Boiling PointNot AvailableNot Available Water Solubility4.52e+00 g/LNot Available LogP0.6Not Available

Predicted Properties

Property Value Source Water Solubility4.52 mg/mLALOGPS logP1.02ALOGPS logP0.73ChemAxon logS-1.7ALOGPS pKa (Strongest Acidic)4.02ChemAxon pKa (Strongest Basic)-1.2ChemAxon Physiological Charge-1ChemAxon Hydrogen Acceptor Count3ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area57.61 ŲChemAxon Rotatable Bond Count3ChemAxon Refractivity54.63 m³·mol^-1ChemAxon Polarizability21.72 ųChemAxon Number of Rings1ChemAxon Bioavailability1ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

Spectra Spectra

Spectrum Type Description Splash Key LC-MS/MS

LC-MS/MS Spectrum – , positivesplash10-014i-0940000000-26ddf220b67fb8dcdff0View in MoNA LC-MS/MS

LC-MS/MS Spectrum – , positivesplash10-01b9-8910000000-d831e8d48402a4c5fe73View in MoNA LC-MS/MS

LC-MS/MS Spectrum – LC-ESI-QFT , positivesplash10-01b9-9720000000-8218e12ef8f7e988c312View in MoNA Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

Biological Properties Cellliar Locations

Cytoplasm

Extracellliar

Membrane

Biofluid Locations

Blood

Urine

Tissue Location

Not Available Pathways

Name SMPDB Link KEGG Link Captopril PathwaySMP00146Not Available

Normal Concentrations

Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01197

21059682

details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01197

21059682

details

Abnormal Concentrations

Not Available Associated Disorders and Diseases Disease References

None Associated OMIM IDs

None External Links DrugBank ID

DB01197 DrugBank Metabolite ID

Not Available Phenol Explorer Compound ID

Not Available Phenol Explorer Metabolite ID

Not Available FoodDB ID

Not Available KNApSAcK ID

Not Available Chemspider ID

40130 KEGG Compound ID

Not Available BioCyc ID

Not Available BiGG ID

Not Available Wikipedia Link

Captopril NuGOwiki Link

HMDB15328 Metagene Link

HMDB15328 METLIN ID

Not Available PubChem Compound

44093 PDB ID

X8Z ChEBI ID

3380

Product: Folinic acid

References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References

1. Atkinson AB, Robertson JI: Captopril in the treatment of clinical hypertension and cardiac failure. Lancet. 1979 Oct 20;2(8147):836-9. [PubMed:90928 ]
2. Patchett AA, Harris E, Tristram EW, Wyvratt MJ, Wu MT, Taub D, Peterson ER, Ikeler TJ, ten Broeke J, Payne LG, Ondeyka DL, Thorsett ED, Greenlee WJ, Lohr NS, Hoffsommer RD, Joshua H, Ruyle WV, Rothrock JW, Aster SD, Maycock AL, Robinson FM, Hirschmann R, Sweet CS, Ulm EH, Gross DM, Vassil TC, Stone CA: A new class of angiotensin-converting enzyme inhibitors. Nature. 1980 Nov 20;288(5788):280-3. [PubMed:6253826 ]
3. Smith CG, Vane JR: The discovery of captopril. FASEB J. 2003 May;17(8):788-9. [PubMed:12724335 ]

Enzymes

General function:

Involved in monooxygenase activity

Specific function:

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.

Gene Name:

CYP2D6

Uniprot ID:

P10635

Molecular weight:

55768.94

References

1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

General function:

Involved in metallopeptidase activity

Specific function:

Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety

Gene Name:

ACE

Uniprot ID:

P12821

Molecular weight:

149713.7

References

1. Andujar-Sanchez M, Jara-Perez V, Camara-Artigas A: Thermodynamic determination of the binding constants of angiotensin-converting enzyme inhibitors by a displacement method. FEBS Lett. 2007 Jul 24;581(18):3449-54. Epub 2007 Jun 27. [PubMed:17618628 ]
2. Dalkas GA, Marchand D, Galleyrand JC, Martinez J, Spyroulias GA, Cordopatis P, Cavelier F: Study of a lipophilic captopril analogue binding to angiotensin I converting enzyme. J Pept Sci. 2010 Feb;16(2):91-7. doi: 10.1002/psc.1201. [PubMed:20014331 ]
3. Natesh R, Schwager SL, Evans HR, Sturrock ED, Acharya KR: Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry. 2004 Jul 13;43(27):8718-24. [PubMed:15236580 ]
4. Piepho RW: Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm. 2000 Oct 1;57 Suppl 1:S3-7. [PubMed:11030016 ]
5. Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. [PubMed:11929321 ]
6. Tzakos AG, Naqvi N, Comporozos K, Pierattelli R, Theodorou V, Husain A, Gerothanassis IP: The molecular basis for the selection of captopril cis and trans conformations by angiotensin I converting enzyme. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5084-7. Epub 2006 Aug 2. [PubMed:16889963 ]
7. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

General function:

Involved in metalloendopeptidase activity

Specific function:

May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide

Gene Name:

MMP9

Uniprot ID:

P14780

Molecular weight:

78457.5

References

1. Okada M, Kikuzuki R, Harada T, Hori Y, Yamawaki H, Hara Y: Captopril attenuates matrix metalloproteinase-2 and -9 in monocrotaline-induced right ventricular hypertrophy in rats. J Pharmacol Sci. 2008 Dec;108(4):487-94. Epub 2008 Dec 5. [PubMed:19057128 ]
2. Reinhardt D, Sigusch HH, Hensse J, Tyagi SC, Korfer R, Figulla HR: Cardiac remodelling in end stage heart failure: upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP. Heart. 2002 Nov;88(5):525-30. [PubMed:12381651 ]
3. Williams RN, Parsons SL, Morris TM, Rowlands BJ, Watson SA: Inhibition of matrix metalloproteinase activity and growth of gastric adenocarcinoma cells by an angiotensin converting enzyme inhibitor in in vitro and murine models. Eur J Surg Oncol. 2005 Nov;31(9):1042-50. Epub 2005 Jul 1. [PubMed:15993560 ]
4. Yamamoto D, Takai S, Miyazaki M: Inhibitory profiles of captopril on matrix metalloproteinase-9 activity. Eur J Pharmacol. 2008 Jul 7;588(2-3):277-9. doi: 10.1016/j.ejphar.2008.04.031. Epub 2008 May 22. [PubMed:18501888 ]

General function:

Involved in metalloendopeptidase activity

Specific function:

PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels

Gene Name:

MMP2

Uniprot ID:

P08253

Molecular weight:

73881.7

References

1. Brower GL, Levick SP, Janicki JS: Inhibition of matrix metalloproteinase activity by ACE inhibitors prevents left ventricular remodeling in a rat model of heart failure. Am J Physiol Heart Circ Physiol. 2007 Jun;292(6):H3057-64. Epub 2007 Feb 16. [PubMed:17308006 ]
2. Okada M, Kikuzuki R, Harada T, Hori Y, Yamawaki H, Hara Y: Captopril attenuates matrix metalloproteinase-2 and -9 in monocrotaline-induced right ventricular hypertrophy in rats. J Pharmacol Sci. 2008 Dec;108(4):487-94. Epub 2008 Dec 5. [PubMed:19057128 ]
3. Prontera C, Mariani B, Rossi C, Poggi A, Rotilio D: Inhibition of gelatinase A (MMP-2) by batimastat and captopril reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma. Int J Cancer. 1999 May 31;81(5):761-6. [PubMed:10328230 ]
4. Reinhardt D, Sigusch HH, Hensse J, Tyagi SC, Korfer R, Figulla HR: Cardiac remodelling in end stage heart failure: upregulation of matrix metalloproteinase (MMP) irrespective of the underlying disease, and evidence for a direct inhibitory effect of ACE inhibitors on MMP. Heart. 2002 Nov;88(5):525-30. [PubMed:12381651 ]
5. Williams RN, Parsons SL, Morris TM, Rowlands BJ, Watson SA: Inhibition of matrix metalloproteinase activity and growth of gastric adenocarcinoma cells by an angiotensin converting enzyme inhibitor in in vitro and murine models. Eur J Surg Oncol. 2005 Nov;31(9):1042-50. Epub 2005 Jul 1. [PubMed:15993560 ]
6. Yamamoto D, Takai S, Hirahara I, Kusano E: Captopril directly inhibits matrix metalloproteinase-2 activity in continuous ambulatory peritoneal dialysis therapy. Clin Chim Acta. 2010 May 2;411(9-10):762-4. doi: 10.1016/j.cca.2010.02.059. Epub 2010 Feb 22. [PubMed:20184869 ]

Transporters

General function:

Involved in ATP binding

Specific function:

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

Gene Name:

ABCB1

Uniprot ID:

P08183

Molecular weight:

141477.3

References

1. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K: Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500. [PubMed:11895100 ]

General function:

Involved in transporter activity

Specific function:

Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products

Gene Name:

SLC15A1

Uniprot ID:

P46059

Molecular weight:

78805.3

References

1. Watanabe K, Sawano T, Terada K, Endo T, Sakata M, Sato J: Studies on intestinal absorption of sulpiride (1): carrier-mediated uptake of sulpiride in the human intestinal cell line Caco-2. Biol Pharm Bull. 2002 Jul;25(7):885-90. [PubMed:12132663 ]
2. Temple CS, Boyd CA: Proton-coupled oligopeptide transport by rat renal cortical brush border membrane vesicles: a functional analysis using ACE inhibitors to determine the isoform of the transporter. Biochim Biophys Acta. 1998 Aug 14;1373(1):277-81. [PubMed:9733984 ]

General function:

Involved in ion transmembrane transporter activity

Specific function:

Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS). Mediates the sodium-independent uptake of p- aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3-azido- 3-deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro- phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2- furanpropionate (CMPF), cidofovir, adefovir, 9-(2- phosphonylmethoxyethyl) guanine (PMEG), 9-(2- phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p- chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid. PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate

Gene Name:

SLC22A6

Uniprot ID:

Q4U2R8

Molecular weight:

61815.8

References

1. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. [PubMed:9880528 ]

PMID: 15163697

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