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Identification
NameRolitetracycline
Accession NumberDB01301
Typesmall molecule
Groupsapproved
Description

A pyrrolidinylmethyl tetracycline. [PubChem]

Structure
Thumb
SynonymsNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
CategoriesNot Available
CAS number751-97-3
WeightAverage: 527.5662
Monoisotopic: 527.226765047
Chemical FormulaC27H33N3O8
InChI KeyInChIKey=HMEYVGGHISAPJR-IAHYZSEUSA-N
InChI
InChI=1S/C27H33N3O8/c1-26(37)13-7-6-8-16(31)17(13)21(32)18-14(26)11-15-20(29(2)3)22(33)19(24(35)27(15,38)23(18)34)25(36)28-12-30-9-4-5-10-30/h6-8,14-15,20,31,33-34,37-38H,4-5,9-12H2,1-3H3,(H,28,36)/t14-,15-,20-,26+,27-/m0/s1
IUPAC Name
(4S,4aS,5aS,6S,12aS)-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-N-(pyrrolidin-1-ylmethyl)-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
SMILES
[H][C@@]12C[C@@]3([H])C(C(=O)C4=C(O)C=CC=C4[C@@]3(C)O)=C(O)[C@]1(O)C(=O)C(C(=O)NCN1CCCC1)=C(O)[C@H]2N(C)C
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassAcenes and Derivatives
SubclassNaphthacenes
Direct parentNaphthacenes
Alternative parentsAnthracenecarboxylic Acids and Derivatives; Anthraquinones; Tetralins; Phenols and Derivatives; Pyrrolidines; Tertiary Alcohols; Polyols; Secondary Carboxylic Acid Amides; Tertiary Amines; Ketones; Enolates; Carboxylic Acids; Enols; Polyamines
Substituentsanthraquinone; tetralin; phenol derivative; benzene; tertiary alcohol; pyrrolidine; carboxamide group; tertiary amine; ketone; polyol; secondary carboxylic acid amide; polyamine; enol; carboxylic acid derivative; enolate; carboxylic acid; amine; alcohol; carbonyl group; organonitrogen compound
Classification descriptionThis compound belongs to the naphthacenes. These are compounds containing a naphthacene moiety, which is a polyaromatic hydrocarbon made of four linearly fused benzene rings.
Pharmacology
IndicationRolitetracycline is a broad-spectrum antibiotic used in cases needing high concentrations or when oral administration is impractical.
PharmacodynamicsNot Available
Mechanism of actionRolitetracycline is a semisynthetic broad-spectrum tetracycline antibiotic used especially for parenteral administration in cases requiring high concentrations or when oral administration is impractical. Rolitetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the 30S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySymptoms of overdose include anorexia, nausea, diarrhoea, glossitis, dysphagia, enterocolitis and inflammatory lesions (with monilial overgrowth) in the anogenital region, skin reactions such as maculopapular and erythematous rashes, exfoliative dermatitis, photosensitivity, hypersensitivity reactions such as urticaria, angioneurotic oedema, anaphylaxis, anaphyl-actoid purpura, pericarditis, and exacerbation of systemic lupus erythematosus, benign intracranial hypertension in adults disappearing on discontinuation of the medicine, haematologic abnormalities such as haemolytic anaemia, thrombocytopenia, neutropenia, and eosinophilia. LD50=262 mg/kg (I.P. in rat).
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.7999
Blood Brain Barrier - 0.9659
Caco-2 permeable - 0.6259
P-glycoprotein substrate Substrate 0.9289
P-glycoprotein inhibitor I Non-inhibitor 0.875
P-glycoprotein inhibitor II Inhibitor 0.7922
Renal organic cation transporter Non-inhibitor 0.7671
CYP450 2C9 substrate Non-substrate 0.7614
CYP450 2D6 substrate Non-substrate 0.7656
CYP450 3A4 substrate Substrate 0.7527
CYP450 1A2 substrate Non-inhibitor 0.9068
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.923
CYP450 2C19 substrate Non-inhibitor 0.8968
CYP450 3A4 substrate Non-inhibitor 0.926
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8647
Ames test Non AMES toxic 0.6931
Carcinogenicity Non-carcinogens 0.9246
Biodegradation Not ready biodegradable 0.6204
Rat acute toxicity 2.7094 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8692
hERG inhibition (predictor II) Inhibitor 0.7194
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubility5.55E+005 mg/LMERCK INDEX (1996)
Predicted Properties
PropertyValueSource
water solubility1.81e+00 g/lALOGPS
logP-0.08ALOGPS
logP-3.8ChemAxon
logS-2.5ALOGPS
pKa (strongest acidic)0.31ChemAxon
pKa (strongest basic)8.24ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count10ChemAxon
hydrogen donor count6ChemAxon
polar surface area170.87ChemAxon
rotatable bond count4ChemAxon
refractivity139.45ChemAxon
polarizability54.05ChemAxon
number of rings5ChemAxon
bioavailability0ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Horacio Alfredo Priestap, Carlos Rappaport, “Process for producing rolitetracycline.” U.S. Patent US3985768, issued September, 1963.

US3985768
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD02282
PubChem Compound5282179
PubChem Substance46507805
ChemSpider4445374
Therapeutic Targets DatabaseDAP000884
PharmGKBPA164779049
WikipediaRolitetracycline
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcitretinIncreased risk of intracranial hypertension
AmoxicillinPossible antagonism of action
AmpicillinPossible antagonism of action
BenzylpenicillinPossible antagonism of action
CarbenicillinPossible antagonism of action
ClavulanatePossible antagonism of action
CloxacillinPossible antagonism of action
DicloxacillinPossible antagonism of action
Ethinyl EstradiolThis anti-infectious agent could decrease the effect of the oral contraceptive
EtretinateIncreased risk of intracranial hypertension
FlucloxacillinPossible antagonism of action
IsotretinoinIncreased risk of intracranial hypertension
Penicillin VPossible antagonism of action
PiperacillinPossible antagonism of action
PivampicillinPossible antagonism of action
PivmecillinamPossible antagonism of action
Food InteractionsNot Available

1. 30S ribosomal protein S9

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
30S ribosomal protein S9 P0A7X3 Details

References:

  1. Carrasco-Pancorbo A, Casado-Terrones S, Segura-Carretero A, Fernandez-Gutierrez A: Reversed-phase high-performance liquid chromatography coupled to ultraviolet and electrospray time-of-flight mass spectrometry on-line detection for the separation of eight tetracyclines in honey samples. J Chromatogr A. 2008 Jun 27;1195(1-2):107-16. Epub 2008 May 10. Pubmed
  2. Griffin MO, Fricovsky E, Ceballos G, Villarreal F: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep;299(3):C539-48. Epub 2010 Jun 30. Pubmed

2. 16S rRNA

Kind: nucleotide

Organism: Enteric bacteria and other eubacteria

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details

References:

  1. Pringle M, Fellstrom C, Johansson KE: Decreased susceptibility to doxycycline associated with a 16S rRNA gene mutation in Brachyspira hyodysenteriae. Vet Microbiol. 2007 Jul 20;123(1-3):245-8. Epub 2007 Feb 25. Pubmed
  2. Kumar S, Kutlin A, Roblin P, Kohlhoff S, Bodetti T, Timms P, Hammerschlag MR: Isolation and antimicrobial susceptibilities of Chlamydial isolates from Western barred bandicoots. J Clin Microbiol. 2007 Feb;45(2):392-4. Epub 2006 Nov 22. Pubmed
  3. Ross JI, Eady EA, Cove JH, Cunliffe WJ: 16S rRNA mutation associated with tetracycline resistance in a gram-positive bacterium. Antimicrob Agents Chemother. 1998 Jul;42(7):1702-5. Pubmed

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

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

Comments
Drug created on June 30, 2007 08:26 / Updated on September 16, 2013 17:14