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Record Information
Version3.6
Creation Date2012-09-06 15:16:51 UTC
Update Date2013-02-09 00:33:19 UTC
HMDB IDHMDB15263
Secondary Accession NumbersNone
Metabolite Identification
Common NameProguanil
DescriptionProguanil is a prophylactic antimalarial drug, which works by stopping the malaria parasite, Plasmodium falciparum and Plasmodium vivax, from reproducing once it is in the red blood cells. It does this by inhibiting the enzyme, dihydrofolate reductase, which is involved in the reproduction of the parasite.
Structure
Thumb
SynonymsNot Available
Chemical FormulaC11H16ClN5
Average Molecular Weight253.731
Monoisotopic Molecular Weight253.109423244
IUPAC Name(E)-1-({amino[(4-chlorophenyl)amino]methylidene}amino)-N'-(propan-2-yl)methenimidamide
Traditional IUPAC Nameproguanil
CAS Registry Number500-92-5
SMILES
CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1
InChI Identifier
InChI=1S/C11H16ClN5/c1-7(2)15-10(13)17-11(14)16-9-5-3-8(12)4-6-9/h3-7H,1-2H3,(H5,13,14,15,16,17)
InChI KeySSOLNOMRVKKSON-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Homomonocyclic Compounds
ClassGuanidines
Sub ClassBiguanides
Other Descriptors
  • Chlorobenzenes
  • Organic Compounds
  • biguanides(ChEBI)
  • organochlorine compound(ChEBI)
Substituents
  • Aryl Chloride
  • Organochloride
  • Polyamine
Direct ParentBiguanides
Ontology
StatusExpected and Not Quantified
Origin
  • Drug
Biofunction
  • Antimalarials
  • Antimetabolites
Application
  • Pharmaceutical
Cellular locations
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point129 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility2.86e-01 g/LNot Available
LogP1.8Not Available
Predicted Properties
PropertyValueSource
water solubility0.29 g/LALOGPS
logP1.9ALOGPS
logP1.89ChemAxon
logS-3ALOGPS
pKa (strongest acidic)19.77ChemAxon
pKa (strongest basic)10.12ChemAxon
physiological charge1ChemAxon
hydrogen acceptor count5ChemAxon
hydrogen donor count3ChemAxon
polar surface area88.79ChemAxon
rotatable bond count2ChemAxon
refractivity71.07ChemAxon
polarizability26.84ChemAxon
Spectra
SpectraNot Available
Biological Properties
Cellular Locations
  • 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 DB01131
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB01131
  • Not Applicable
details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB01131
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID4754
KEGG Compound IDC07631
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkProguanil
NuGOwiki LinkHMDB15263
Metagene LinkHMDB15263
METLIN IDNot Available
PubChem Compound4923
PDB IDNot Available
ChEBI ID8455
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in dihydrofolate reductase activity
Specific function:
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA and that of DHFRL1.
Gene Name:
DHFR
Uniprot ID:
P00374
Molecular weight:
21452.61
References
  1. Kaneko A, Bergqvist Y, Takechi M, Kalkoa M, Kaneko O, Kobayakawa T, Ishizaki T, Bjorkman A: Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil. J Infect Dis. 1999 Apr;179(4):974-9. Pubmed: 10068594
  2. Vasconcelos KF, Plowe CV, Fontes CJ, Kyle D, Wirth DF, Pereira da Silva LH, Zalis MG: Mutations in Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase of isolates from the Amazon region of Brazil. Mem Inst Oswaldo Cruz. 2000 Sep-Oct;95(5):721-8. Pubmed: 10998224
  3. Tahar R, de Pecoulas PE, Basco LK, Chiadmi M, Mazabraud A: Kinetic properties of dihydrofolate reductase from wild-type and mutant Plasmodium vivax expressed in Escherichia coli. Mol Biochem Parasitol. 2001 Apr 6;113(2):241-9. Pubmed: 11295178
  4. Durand R, Jafari S, Bouchaud O, Ralaimazava P, Keundjian A, Le Bras J: Plasmodium falciparum: pfcrt and DHFR mutations are associated with failure of chloroquine plus proguanil prophylaxis in travelers. J Infect Dis. 2001 Dec 15;184(12):1633-4. Pubmed: 11740746
  5. Le Bras J, Durand R: The mechanisms of resistance to antimalarial drugs in Plasmodium falciparum. Fundam Clin Pharmacol. 2003 Apr;17(2):147-53. Pubmed: 12667224
  6. 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 monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
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. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular weight:
55944.565
References
  1. Lu AH, Shu Y, Huang SL, Wang W, Ou-Yang DS, Zhou HH: In vitro proguanil activation to cycloguanil is mediated by CYP2C19 and CYP3A4 in adult Chinese liver microsomes. Acta Pharmacol Sin. 2000 Aug;21(8):747-52. Pubmed: 11501186
  2. 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. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular weight:
56848.42
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. Epub 2009 Nov 24. Pubmed: 19934256
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. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
Gene Name:
CYP1A2
Uniprot ID:
P05177
Molecular weight:
58406.915
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. Epub 2009 Nov 24. Pubmed: 19934256