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{{Short description|Chemical compound}} |
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{{Drugbox |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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| verifiedrevid = 443265716 |
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{{Infobox drug |
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| verifiedrevid = 447815338 |
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| IUPAC_name = (3''R'',5''R'',6''S'',7''R'',8''R'',11''R'',12''S'',13''R'',14''S'',15''S'')-14-((2''S'',3''R'',4''S'',6''R'')-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2''H''-pyran-2-yloxy)-6-hydroxy-12-((2''R'',4''S'',5''S'',6''S'')-5-hydroxy-4-methoxy-6-methyltetrahydro-2''H''-pyran-2-yloxy)-5,7,8,11,13,15-hexamethyl-1,9-dioxaspirohexadecane-4,10-dione |
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| IUPAC_name = (3''R'',5''R'',6''S'',7''R'',8''R'',11''R'',12''S'',13''R'',14''S'',15''S'')-14-((2''S'',3''R'',4''S'',6''R'')-4-(dimethylamino)-3-hydroxy-6-methyltetrahydro-2''H''-pyran-2-yloxy)-6-hydroxy-12-((2''R'',4''S'',5''S'',6''S'')-5-hydroxy-4-methoxy-6-methyltetrahydro-2''H''-pyran-2-yloxy)-5,7,8,11,13,15-hexamethyl-1,9-dioxaspirohexadecane-4,10-dione |
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| image = Oleandomycin.png |
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| image = Oleandomycin.svg |
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<!--Clinical data--> |
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<!--Clinical data--> |
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| tradename = |
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| tradename = |
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| Drugs.com = {{drugs.com|international|oleandomycin}} |
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| Drugs.com = {{drugs.com|international|oleandomycin}} |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_US = <!-- A / B / C / D / X --> |
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| pregnancy_category = |
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| pregnancy_category = |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> |
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| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V --> |
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<!--Pharmacokinetic data--> |
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<!--Pharmacokinetic data--> |
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| bioavailability = |
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| bioavailability = |
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| protein_bound = |
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| metabolism = |
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| metabolism = |
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| excretion = |
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<!--Identifiers--> |
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<!--Identifiers--> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 3922-90-5 |
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| CAS_number = 3922-90-5 |
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| ATC_prefix = J01 |
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| ATC_prefix = J01 |
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| ATC_suffix = FA05 |
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| ATC_suffix = FA05 |
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| PubChem = 5284598 |
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| PubChem = 5284598 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 606258 |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = |
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| DrugBank = |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 4447646 |
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| ChemSpiderID = 4447646 |
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<!--Chemical data--> |
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<!--Chemical data--> |
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| C=35 | H=61 | N=1 | O=12 |
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| C=35 | H=61 | N=1 | O=12 |
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| molecular_weight = 687.858 g/mol |
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| smiles = O=C4(C)(O)(C)(OC(=O)((O1O((O)(OC)C1)C)(C)(O2O(C)C(N(C)C)2O)(C)C43OC3)C)C |
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| smiles = O=C4(C)(O)(C)(OC(=O)((O1O((O)(OC)C1)C)(C)(O2O(C)C(N(C)C)2O)(C)C43OC3)C)C |
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| InChI = 1/C35H61NO12/c1-16-14-35(15-43-35)32(40)19(4)27(37)18(3)22(7)46-33(41)21(6)31(47-26-13-25(42-11)28(38)23(8)45-26)20(5)30(16)48-34-29(39)24(36(9)10)12-17(2)44-34/h16-31,34,37-39H,12-15H2,1-11H3/t16-,17+,18-,19+,20+,21+,22+,23-,24-,25-,26-,27-,28-,29+,30-,31-,34-,35-/m0/s1 |
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| InChIKey = RZPAKFUAFGMUPI-KGIGTXTPBQ |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C35H61NO12/c1-16-14-35(15-43-35)32(40)19(4)27(37)18(3)22(7)46-33(41)21(6)31(47-26-13-25(42-11)28(38)23(8)45-26)20(5)30(16)48-34-29(39)24(36(9)10)12-17(2)44-34/h16-31,34,37-39H,12-15H2,1-11H3/t16-,17+,18-,19+,20+,21+,22+,23-,24-,25-,26-,27-,28-,29+,30-,31-,34-,35-/m0/s1 |
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| StdInChI = 1S/C35H61NO12/c1-16-14-35(15-43-35)32(40)19(4)27(37)18(3)22(7)46-33(41)21(6)31(47-26-13-25(42-11)28(38)23(8)45-26)20(5)30(16)48-34-29(39)24(36(9)10)12-17(2)44-34/h16-31,34,37-39H,12-15H2,1-11H3/t16-,17+,18-,19+,20+,21+,22+,23-,24-,25-,26-,27-,28-,29+,30-,31-,34-,35-/m0/s1 |
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'''Oleandomycin''' is a ] antibiotic. It is synthesized from strains of ''Streptomyces antibioticus''. It is weaker than ]. |
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'''Oleandomycin''' is a ] antibiotic. It is synthesized from strains of ''Streptomyces antibioticus''. It is weaker than ]. |
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It used to be sold under the brand name '''Sigmamycine''', combined with ], and made by the company '''Rosa-Phytopharma''' in ]. |
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It used to be sold under the brand name '''Sigmamycine''', combined with ], and made by the company '''Rosa-Phytopharma''' in ]. |
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== Medical uses == |
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Oleandomycin inhibits the bacteria responsible for upper respiratory tract infections. Its spectrum of activity includes bacteria in the '']'' and '']'' genera.{{citation needed|date=March 2023}} |
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The MIC for oleandomycin is 0.3-3 μg/mL for ''Staphylococcus aureus''.<ref name=Semenitz>{{cite journal | vauthors = Semenitz E | title = The antibacterial activity of oleandomycin and erythromycin--a comparative investigation using microcalorimetry and MIC determination | journal = The Journal of Antimicrobial Chemotherapy | volume = 4 | issue = 5 | pages = 455–7 | date = September 1978 | pmid = 690046 | doi = 10.1093/jac/4.5.455 }}</ref> |
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{{Macrolides, lincosamides and streptogramins}} |
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Oleandomycin is approved as a veterinary antibiotic in some countries. |
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] |
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It has been approved as a swine and poultry antibiotic in the United States. However, it is currently only approved in the United States for production uses.<ref>{{cite web |url= https://www.fda.gov/downloads/AnimalVeterinary/DevelopmentApprovalProcess/UCM482258.pdf |title= Drugs Transitioning from Over-the-Counter (OTC) to Veterinary Feed Directive (VFD) Status |author=<!--Staff writer(s); no by-line.--> |date=19 Jan 2016 |publisher=U.S. Food and Drug Administration |access-date=11 May 2016}} |
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</ref><ref>{{cite web |url=https://www.law.cornell.edu/cfr/text/21/558.435 |
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|title=21 CFR 558.435 - Oleandomycin. |author=<!--Staff writer(s); no by-line.--> |date=17 Sep 2001 |website=Legal Information Institute |publisher=Cornell University Law School |access-date=11 May 2016}}</ref> |
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==Pharmacology== |
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===Mechanism of action=== |
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{{antibiotic-stub}} |
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Oleandomycin is a bacteriostatic agent. Like erythromycin, oleandomycin binds to the 50s subunit of bacterial ribosomes, inhibiting the completion of proteins vital to survival and replication. |
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It interferes with translational activity but also with 50s subunit formation.{{citation needed|date=March 2023}} |
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However, unlike erythromycin and its effective synthetic derivatives, it lacks a 12-hydroxyl group and a 3-methoxy group. This change in structure may adversely affect its interactions with 50S structures and explain why it is a less powerful antibiotic.<ref>{{cite journal | vauthors = Champney WS, Tober CL, Burdine R | title = A comparison of the inhibition of translation and 50S ribosomal subunit formation in Staphylococcus aureus cells by nine different macrolide antibiotics | journal = Current Microbiology | volume = 37 | issue = 6 | pages = 412–7 | date = December 1998 | pmid = 9806980 | doi = 10.1007/s002849900402 | s2cid = 22322878 }}</ref> |
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===Relative strength=== |
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Oleandomycin is far less effective than erythromycin in bacterial minimum inhibitory concentration tests involving staphylococci or enterococci.<ref name=Semenitz/> |
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However, macrolide antibiotics can accumulate in organs or cells and this effect can prolong the bioactivity of this category of antibiotics even if its concentration in plasma is below what is considered capable of a therapeutic effect.{{citation needed|date=March 2023}} |
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==Chemistry== |
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=== Polyketide biosynthesis === |
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{{See also|Polyketide synthase}} |
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] |
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The oleandomycin synthase (OLES) follows the module structure of a type I synthase. The polyketide chain is bound through thioester linkages to the S-H groups of the ACP and KS domains {{citation needed|date=March 2023}} |
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* The gene cluster OLES1 codes for modules 0-2, module 0 containing an acetyl-CoA starter unit and all remaining moduless carrying a methyl malonyl-CoA elongation unit attached to its keto synthase unit. |
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* OLES2 codes for modules 3 and 4. Module 3 is notable for potentially carrying a redox-inactive ketoreductase that is responsible for retaining the unreduced carbonyl adjacent to carbon 8. |
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* OLES3 codes for modules 5 and 6. |
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The amino acid sequence similarities between OLES and ] (erythromycin precursor synthase) show only a 45% common identity. Note that unlike in the erythromycin precursor synthase, there is a KS in the loading domain of OLES.<ref name =Rawlings>{{cite journal | vauthors = Rawlings BJ | title = Type I polyketide biosynthesis in bacteria (part B) | journal = Natural Product Reports | volume = 18 | issue = 3 | pages = 231–81 | date = June 2001 | pmid = 11476481 | doi = 10.1039/b100191o }}</ref> |
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=== Post-PKS modifications === |
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] |
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The genes OleG1 and G2 are responsible for the glycosyltransferases that attach oleandomycin's characteristic sugars to the macrolide. These sugars are derived from ]. OLEG1 transfers dTDP-D-desoamine and OleG2 transfers D-TDP-L-] to the macrolide ring. The epoxidation that occurs afterwards is from the enzyme encoded by OleP, which could be homologous with a P450 enzyme. The method by which OleP epoxidates is suspected to be a dihydroxylation followed by the conversion of a hydroxyl group into a phosphate group that then leaves via a nucleophilic ring closure by the other hydroxyl group.<ref name=Rawlings/> |
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{{clear}} |
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==History== |
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Oleandomycin was first discovered as a product of the bacterium ''Streptomyces antibioticus'' in 1954 by Dr. Sobin, English, and Celmer. In 1960, Hochstein successfully managed to determine the structure of oleandomycin.<ref>{{cite journal | vauthors = Hochstein FA, Els H, Celmer WD, Shapiro BL, Woodward RB | title = The Structure of Oleandomycin | journal = Journal of the American Chemical Society | volume = 82 | issue = 12 | pages = 3225–3227 | date = June 1960 | doi = 10.1021/ja01497a066 | bibcode = 1960JAChS..82.3225H }}</ref> This macrolide was discovered at around the same time as its relatives erythromycin and spiramycin.<ref name=Garrod>{{cite journal | vauthors = Garrod LP | title = The erythromycin group of antibiotics | journal = British Medical Journal | volume = 2 | issue = 5036 | pages = 57–63 | date = July 1957 | pmid = 13436854 | pmc = 1961747 | doi = 10.1136/bmj.2.5036.57 | jstor = 25383104 }}</ref> |
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=== Sigmamycine combination drug === |
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Public interest in oleandomycin peaked when ] introduced the combination drug Sigmamycine into the market in 1956. Sigmamycine was a combination drug of oleandomycin and tetracycline that was supported by a major marketing campaign. It was in fact claimed that a 2:1 mixture of tetracycline and oleandomycin had a synergistic effect on staphylococci. It was also claimed that the mixture would be effective on organisms that are mostly resistant to tetracycline or oleandomycin alone. Both of these claims were refuted by findings such as those by Lawrence P. Garrod that could find no evidence that such claims were properly substantiated.<ref name=Garrod/> By the early 1970s, Pfizer's combination drugs were withdrawn from the market. |
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<ref>{{cite journal | vauthors = Podolsky SH, Greene JA | title = Combination drugs--hype, harm, and hope | journal = The New England Journal of Medicine | volume = 365 | issue = 6 | pages = 488–91 | date = August 2011 | pmid = 21830965 | doi = 10.1056/NEJMp1106161 }}</ref> |
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<ref>{{cite journal | vauthors = Jones WF, Finland M | title = Antibiotic combinations; tetracycline, erythromycin, oleandomycin and spiramycin and combinations of tetracycline with each of the other three agents; comparisons of activity in vitro and antibacterial action of blood after oral administration | journal = The New England Journal of Medicine | volume = 257 | issue = 12 | pages = 536–47 concl | date = September 1957 | pmid = 13464978 | doi = 10.1056/NEJM195709192571202 }}</ref> |
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<ref>{{cite court |litigants=Pfizer Inc v. L. Richardson c. |vol= 434 |reporter=vF.2D |opinion=536 |pinpoint=8 |court=United States Court of Appeals, Second Circuit |date=2 Nov 1970 |url=http://openjurist.org/434/f2d/536/pfizer-inc-v-l-richardson-c |access-date= 6 May 2016}}</ref> |
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== Society and culture == |
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===Brand names=== |
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* Mastalone – Oleandomycin, oxatetracycline, neomycin – Zoetis Australia and Pfizer Animal Health |
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* Mastiguard – Oleandomycin, oxatetracycline – Stockguard Animal Health<ref>{{cite web |url=https://www.drugs.com/international/oleandomycin.html |
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|title=Oleandomycin |author=<!--Staff writer(s); no by-line.--> |date=16 April 2010 |website=Drugs.com |access-date=11 May 2016}}</ref> |
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* Formerly sold as Sigmamycine by Pfizer (Oleandomycin + ] + ]) |
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== References == |
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{{reflist}} |
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{{Macrolides, lincosamides and streptogramins}} |
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