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Identification
Name Rolitetracycline
Accession Number DB01301
Type small molecule
Groups approved
Description

A pyrrolidinylmethyl tetracycline. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Anti-Bacterial Agents
  • Tetracyclines
CAS number 751-97-3
Weight Average: 527.5662
Monoisotopic: 527.226765047
Chemical Formula C27H33N3O8
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Tetracyclines
Substructures
  • Tetracyclines
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Naphthalenes
  • Phenols and Derivatives
  • Amino Ketones
  • Phenylpropenes
  • Pyrrolidines
  • Benzene and Derivatives
  • Aminals and Derivatives
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Aromatic compounds
  • Cinnamaldehydes
  • Ketenes and Derivatives
  • Phenyl Esters
  • Enols
  • Ketones
Pharmacology
Indication Rolitetracycline is a broad-spectrum antibiotic used in cases needing high concentrations or when oral administration is impractical.
Pharmacodynamics Not Available
Mechanism of action Rolitetracycline 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Symptoms 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 organisms Not Available
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
water solubility 5.55E+005 mg/L MERCK INDEX (1996)
Predicted Properties
Property Value Source
water solubility 1.81e+00 g/l ALOGPS
logP -0.08 ALOGPS
logP -3.8 ChemAxon
logS -2.5 ALOGPS
pKa (strongest acidic) 0.31 ChemAxon
pKa (strongest basic) 8.24 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 10 ChemAxon
hydrogen donor count 6 ChemAxon
polar surface area 170.87 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 139.45 ChemAxon
polarizability 54.05 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02282 Link_out
PubChem Compound 5282179 Link_out
PubChem Substance 46507805 Link_out
ChemSpider 4445374 Link_out
Therapeutic Targets Database DAP000884 Link_out
PharmGKB PA164779049 Link_out
Wikipedia http://en.wikipedia.org/wiki/Rolitetracycline Link_out
ATC Codes
  • J01AA09
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Acitretin Increased risk of intracranial hypertension
Amoxicillin Possible antagonism of action
Ampicillin Possible antagonism of action
Carbenicillin Possible antagonism of action
Clavulanate Possible antagonism of action
Cloxacillin Possible antagonism of action
Dicloxacillin Possible antagonism of action
Ethinyl Estradiol This anti-infectious agent could decrease the effect of the oral contraceptive
Etretinate Increased risk of intracranial hypertension
Flucloxacillin Possible antagonism of action
Isotretinoin Increased risk of intracranial hypertension
Penicillin G Possible antagonism of action
Penicillin V Possible antagonism of action
Piperacillin Possible antagonism of action
Pivampicillin Possible antagonism of action
Pivmecillinam Possible antagonism of action
Food Interactions Not Available
Targets

1. 30S ribosomal protein S9

Pharmacological action: yes
Actions: inhibitor

The C-terminal tail plays a role in the affinity of the 30S P site for different tRNAs. Mutations that decrease this affinity are suppressed in the 70S ribosome

Organism class: bacterial
UniProt ID: P0A7X3 Link_out
Gene: rpsI
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: yes
Actions: inhibitor

In prokaryotes, the 16S rRNA is essential for recognizing the 5' end of mRNA and hence positioning it correctly on the ribosome. The 16S rRNA has a characteristic secondary structure in which half of the nucleotides are base-paired. The 16S rRNA sequence has been highly conserved and is often used for evolutionary and species comparative analysis.

Gene Sequence: FASTA

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
Enzymes

1. Cytochrome P450 3A4

Actions: inhibitor

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. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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 February 08, 2013 16:20