Identification
NameTroleandomycin
Accession NumberDB13179  (DB01361)
TypeSmall Molecule
GroupsApproved
Description

A macrolide antibiotic that is similar to erythromycin.

Structure
Thumb
SynonymsNot Available
External IDs NSC-108166
Product Ingredients Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
TaoNot Available
TriocetinNot Available
Brand mixturesNot Available
Categories
UNIIC4DZ64560D
CAS number2751-09-9
WeightAverage: 813.9684
Monoisotopic: 813.451070479
Chemical FormulaC41H67NO15
InChI KeyLQCLVBQBTUVCEQ-QTFUVMRISA-N
InChI
InChI=1S/C41H67NO15/c1-19-17-41(18-49-41)38(46)23(5)34(53-27(9)43)21(3)25(7)52-39(47)24(6)35(56-32-16-31(48-14)36(26(8)51-32)54-28(10)44)22(4)33(19)57-40-37(55-29(11)45)30(42(12)13)15-20(2)50-40/h19-26,30-37,40H,15-18H2,1-14H3/t19-,20+,21-,22+,23+,24+,25+,26-,30-,31-,32-,33-,34-,35-,36-,37+,40-,41+/m0/s1
IUPAC Name
(3R,5R,6S,7S,8R,11R,12S,13R,14S,15S)-14-{[(2S,3R,4S,6R)-3-(acetyloxy)-4-(dimethylamino)-6-methyloxan-2-yl]oxy}-12-{[(2R,4S,5S,6S)-5-(acetyloxy)-4-methoxy-6-methyloxan-2-yl]oxy}-5,7,8,11,13,15-hexamethyl-4,10-dioxo-1,9-dioxaspiro[2.13]hexadecan-6-yl acetate
SMILES
Pharmacology
Indication

For the treatment of bacterial infection.

Structured Indications Not Available
Pharmacodynamics

Troleandomycin, like other macrolide antibiotics, inhibits bacterial protein synthesis to prevent growth.

Mechanism of action

As a macrolide, troleandomycin binds to the 50S subunit of the bacterial ribosome [2]. This binding inhibits translocation of tRNA along the A, P, and E sites of the ribosome. With tRNA unable to move from site to site, amino acids cannot be deposited onto the polypeptide chain leading to failure of protein synthesis. Bacterial cell growth and duplication is inhibited without the ability to generate the necessary proteins.

TargetKindPharmacological actionActionsOrganismUniProt ID
50S ribosomal protein L32Proteinyes
inhibitor
Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / LMG 4051 / NBRC 15346 / NCIMB 9279 / R1 / VKM B-1422)P49228 details
50S ribosomal protein L4Proteinyes
inhibitor
Escherichia coli (strain K12)P60723 details
Nuclear receptor subfamily 1 group I member 2Proteinunknown
activator
HumanO75469 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
Toxicity

Troleandomycin inhibits clearance of theophylline and can increase the likelyhood of toxicity in patients recieving theophylline therapy [1].

Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions Not Available
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Weinberger M, Hudgel D, Spector S, Chidsey C: Inhibition of theophylline clearance by troleandomycin. J Allergy Clin Immunol. 1977 Mar;59(3):228-31. [PubMed:300083 ]
  2. 5. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 614, 631-632). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8 ]
External Links
ATC CodesJ01FA08 — Troleandomycin
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (52.3 KB)
Clinical Trials
Clinical Trials Not Available
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)812.49MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0192 mg/mLALOGPS
logP3.76ALOGPS
logP4.3ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)16.75ChemAxon
pKa (Strongest Basic)7.87ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count12ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area184.19 Å2ChemAxon
Rotatable Bond Count12ChemAxon
Refractivity201.15 m3·mol-1ChemAxon
Polarizability86.08 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9048
Blood Brain Barrier-0.945
Caco-2 permeable-0.522
P-glycoprotein substrateSubstrate0.662
P-glycoprotein inhibitor IInhibitor0.9188
P-glycoprotein inhibitor IINon-inhibitor0.631
Renal organic cation transporterNon-inhibitor0.8177
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7407
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9075
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9223
Ames testAMES toxic0.5213
CarcinogenicityNon-carcinogens0.8564
BiodegradationNot ready biodegradable0.9949
Rat acute toxicity2.2177 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9881
hERG inhibition (predictor II)Non-inhibitor0.9163
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MSNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as aminoglycosides. These are molecules or a portion of a molecule composed of amino-modified sugars.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbohydrates and carbohydrate conjugates
Direct ParentAminoglycosides
Alternative ParentsTetracarboxylic acids and derivatives / Macrolides and analogues / O-glycosyl compounds / Oxanes / Monosaccharides / Trialkylamines / Amino acids and derivatives / Carboxylic acid esters / Ketones / Lactones
SubstituentsAminoglycoside core / Macrolide / Tetracarboxylic acid or derivatives / Glycosyl compound / O-glycosyl compound / Monosaccharide / Oxane / Amino acid or derivatives / Carboxylic acid ester / Ketone
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptorsepoxide, macrolide antibiotic, acetate ester, monosaccharide derivative, polyketide, semisynthetic derivative (CHEBI:45735 ) / Macrolides and lactone polyketides (C12753 ) / Macrolides and lactone polyketides (LMPK04000042 )

Targets

Kind
Protein
Organism
Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / LMG 4051 / NBRC 15346 / NCIMB 9279 / R1 / VKM B-1422)
Pharmacological action
yes
Actions
inhibitor
General Function:
Structural constituent of ribosome
Specific Function:
Forms a cluster with L17 and L22, and with L22, a pair of "tweezers" that hold together all the domains of the 23S rRNA. Interacts with the antibiotic troleandomycin which blocks the peptide exit tunnel.
Gene Name:
rpmF
Uniprot ID:
P49228
Uniprot Name:
50S ribosomal protein L32
Molecular Weight:
6791.905 Da
References
  1. Scharre KA, Eckels DD, Gershwin ME: Depression of colony formation by human thymus-derived lymphocytes with rifampin and other antimicrobial agents. J Infect Dis. 1981 Jun;143(6):832-5. [PubMed:6972981 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
One of the primary rRNA binding proteins, this protein initially binds near the 5'-end of the 23S rRNA (PubMed:3298242). It is important during the early stages of 50S assembly (PubMed:3298242). It makes multiple contacts with different domains of the 23S rRNA in the assembled 50S subunit and ribosome (PubMed:7556101, PubMed:6170935).
Specific Function:
Bacterial-type rna polymerase transcriptional repressor activity, sequence-specific dna binding
Gene Name:
rplD
Uniprot ID:
P60723
Uniprot Name:
50S ribosomal protein L4
Molecular Weight:
22086.36 Da
References
  1. Scharre KA, Eckels DD, Gershwin ME: Depression of colony formation by human thymus-derived lymphocytes with rifampin and other antimicrobial agents. J Infect Dis. 1981 Jun;143(6):832-5. [PubMed:6972981 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
activator
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and is...
Gene Name:
NR1I2
Uniprot ID:
O75469
Uniprot Name:
Nuclear receptor subfamily 1 group I member 2
Molecular Weight:
49761.245 Da
References
  1. Kobayashi K, Yamagami S, Higuchi T, Hosokawa M, Chiba K: Key structural features of ligands for activation of human pregnane X receptor. Drug Metab Dispos. 2004 Apr;32(4):468-72. [PubMed:15039302 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Steroid hydroxylase 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, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Uniprot Name:
Cytochrome P450 2C9
Molecular Weight:
55627.365 Da
References
  1. Ono S, Hatanaka T, Hotta H, Satoh T, Gonzalez FJ, Tsutsui M: Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. Xenobiotica. 1996 Jul;26(7):681-93. [PubMed:8819299 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase 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
Uniprot Name:
Cytochrome P450 2C19
Molecular Weight:
55930.545 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Oxygen binding
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.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Uniprot Name:
Cytochrome P450 3A5
Molecular Weight:
57108.065 Da
References
  1. Klees TM, Sheffels P, Dale O, Kharasch ED: Metabolism of alfentanil by cytochrome p4503a (cyp3a) enzymes. Drug Metab Dispos. 2005 Mar;33(3):303-11. Epub 2004 Nov 22. [PubMed:15557344 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Monooxygenase activity
Specific Function:
Exhibits low testosterone 6-beta-hydroxylase activity.
Gene Name:
CYP3A43
Uniprot ID:
Q9HB55
Uniprot Name:
Cytochrome P450 3A43
Molecular Weight:
57669.21 Da
References
  1. Ledirac N, de Sousa G, Fontaine F, Agouridas C, Gugenheim J, Lorenzon G, Rahmani R: Effects of macrolide antibiotics on CYP3A expression in human and rat hepatocytes: interspecies differences in response to troleandomycin. Drug Metab Dispos. 2000 Dec;28(12):1391-3. [PubMed:11095572 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Gene Name:
CYP2A6
Uniprot ID:
P11509
Uniprot Name:
Cytochrome P450 2A6
Molecular Weight:
56501.005 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase 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.
Gene Name:
CYP2C18
Uniprot ID:
P33260
Uniprot Name:
Cytochrome P450 2C18
Molecular Weight:
55710.075 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase 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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme...
Gene Name:
CYP2C8
Uniprot ID:
P10632
Uniprot Name:
Cytochrome P450 2C8
Molecular Weight:
55824.275 Da
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 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Vitamin d3 25-hydroxylase 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 xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Uniprot Name:
Cytochrome P450 3A4
Molecular Weight:
57342.67 Da
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 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Uniprot Name:
Multidrug resistance protein 1
Molecular Weight:
141477.255 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [PubMed:11716514 ]
  2. Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. [PubMed:11961113 ]
  3. Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. [PubMed:12235267 ]
Drug created on July 06, 2007 13:54 / Updated on September 01, 2017 12:29