Identification

Name
Troleandomycin
Accession Number
DB13179  (DB01361)
Type
Small Molecule
Groups
Approved
Description

A macrolide antibiotic that is similar to erythromycin.

Structure
Thumb
Synonyms
  • Oleandocetine
  • Oleandomycin triacetate
  • Oleandomycin triacetyl ester
  • Triacetyloleandomycin
  • Triacetyloleandomycinum
  • Tribiocillina
  • Troleandomicina
  • Troleandomycine
External IDs
NSC-108166
International/Other Brands
Tao / Triocetin
Categories
UNII
C4DZ64560D
CAS number
2751-09-9
Weight
Average: 813.9684
Monoisotopic: 813.451070479
Chemical Formula
C41H67NO15
InChI Key
LQCLVBQBTUVCEQ-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
CO[C@H]1C[C@H](O[C@H]2[C@H](C)[C@@H](O[C@@H]3O[C@H](C)C[C@@H]([C@H]3OC(C)=O)N(C)C)[C@@H](C)C[C@@]3(CO3)C(=O)[C@H](C)[C@@H](OC(C)=O)[C@@H](C)[C@@H](C)OC(=O)[C@@H]2C)O[C@@H](C)[C@@H]1OC(C)=O

Pharmacology

Indication

For the treatment of bacterial infection.

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.

TargetActionsOrganism
A50S ribosomal protein L32
inhibitor
Deinococcus radiodurans (strain ATCC 13939 / DSM 20539 / JCM 16871 / LMG 4051 / NBRC 15346 / NCIMB 9279 / R1 / VKM B-1422)
A50S ribosomal protein L4
inhibitor
Escherichia coli (strain K12)
UNuclear receptor subfamily 1 group I member 2
activator
Human
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

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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcebutololThe serum concentration of Acebutolol can be increased when it is combined with Troleandomycin.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Troleandomycin.
AcetaminophenThe metabolism of Acetaminophen can be decreased when combined with Troleandomycin.
Acetyl sulfisoxazoleThe metabolism of Troleandomycin can be decreased when combined with Acetyl sulfisoxazole.
Acetylsalicylic acidThe serum concentration of Acetylsalicylic acid can be increased when it is combined with Troleandomycin.
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Troleandomycin.
AgmatineThe metabolism of Agmatine can be decreased when combined with Troleandomycin.
AlclometasoneThe metabolism of Alclometasone can be decreased when combined with Troleandomycin.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Troleandomycin.
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Troleandomycin.
Food Interactions
Not Available

References

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
Human Metabolome Database
HMDB0015448
KEGG Drug
D01322
KEGG Compound
C12753
PubChem Compound
202225
PubChem Substance
347829281
ChemSpider
16707
BindingDB
50370258
ChEBI
45735
ChEMBL
CHEMBL564085
Therapeutic Targets Database
DAP000411
PharmGKB
PA127840611
HET
TAO
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Troleandomycin
ATC Codes
J01FA08 — Troleandomycin
MSDS
Download (52.3 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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)19.62ChemAxon
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
Polarizability86.05 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
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Carbohydrates and carbohydrate conjugates
Direct Parent
Aminoglycosides
Alternative Parents
Tetracarboxylic acids and derivatives / Macrolides and analogues / O-glycosyl compounds / Oxanes / Monosaccharides / Trialkylamines / Amino acids and derivatives / Carboxylic acid esters / Ketones / Lactones
show 7 more
Substituents
Aminoglycoside core / Macrolide / Tetracarboxylic acid or derivatives / Glycosyl compound / O-glycosyl compound / Monosaccharide / Oxane / Amino acid or derivatives / Carboxylic acid ester / Ketone
show 18 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
epoxide, 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 t...
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 an...
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
Actions
Inhibitor
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 un...
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]
  2. Drug Interactions & Labeling - FDA [Link]
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 un...
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
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. Const...
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 un...
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 un...
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]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Details
7. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Drug Interactions & Labeling - FDA [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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 un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions & Labeling - FDA [Link]

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 15, 2018 18:23