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{{chembox {{chembox
| Verifiedfields = changed | Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 400315015
| verifiedrevid = 408764013
| Name = Monensin A
| ImageFile = Monensin A.svg | Name = Monensin A
| ImageFile = Monensin A.svg
| ImageSize = | ImageSize =
| PIN = (2''S'',3''R'',4''S'')-4--3′-methyl-5-yl}-9-hydroxy-2,8-dimethyl-1,6-dioxaspirodecan-7-yl]-3-methoxy-2-methylpentanoic acid
| IUPACName = 4-[2-[5-ethyl-5-[5-[6-hydroxy-6-
| OtherNames = Monensic acid
(hydroxymethyl)-3,5-dimethyl-oxan-2-yl]-
|Section1={{Chembox Identifiers
3-methyl-oxolan-2-yl]oxolan-2-yl]-
| UNII_Ref = {{fdacite|changed|FDA}}
9-hydroxy-2,8-dimethyl-1,6-dioxasp
| UNII = 906O0YJ6ZP
irodec-7-yl]-3-methoxy-2-methyl-
| ChEBI_Ref = {{ebicite|changed|EBI}}
pentanoic acid
| ChEBI = 27617
| OtherNames = monensic acid
| SMILES = O=C(O)(C)(OC)(C)5O1(O(C)(CC1)2O(CC)(CC2)4O(3O(O)(CO)(C3C)C)C4C)C(O)5C
| Section1 = {{Chembox Identifiers
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| SMILES = O=C(O)(C)(OC)(C)5O1(O(C)(CC1)2O(CC)(CC2)4O(3O(O)(CO)(C3C)C)C4C)C(O)5C
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 389937 | ChemSpiderID = 389937
| PubChem = 441145 | PubChem = 441145
| InChI = 1/C36H62O11/c1-10-34(31-20(3)16-26(43-31)28-19(2)15-21(4)36(41,18-37)46-28)12-11-27(44-34)33(8)13-14-35(47-33)17-25(38)22(5)30(45-35)23(6)29(42-9)24(7)32(39)40/h19-31,37-38,41H,10-18H2,1-9H3,(H,39,40)/t19-,20-,21+,22+,23-,24-,25-,26+,27+,28-,29+,30-,31+,33-,34-,35+,36-/m0/s1 | InChI = 1/C36H62O11/c1-10-34(31-20(3)16-26(43-31)28-19(2)15-21(4)36(41,18-37)46-28)12-11-27(44-34)33(8)13-14-35(47-33)17-25(38)22(5)30(45-35)23(6)29(42-9)24(7)32(39)40/h19-31,37-38,41H,10-18H2,1-9H3,(H,39,40)/t19-,20-,21+,22+,23-,24-,25-,26+,27+,28-,29+,30-,31+,33-,34-,35+,36-/m0/s1
| InChIKey = GAOZTHIDHYLHMS-KEOBGNEYBF | InChIKey = GAOZTHIDHYLHMS-KEOBGNEYBF
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 256105 | ChEMBL = 256105
| StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI_Ref = {{stdinchicite|correct|chemspider}}
Line 24: Line 25:
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = GAOZTHIDHYLHMS-KEOBGNEYSA-N | StdInChIKey = GAOZTHIDHYLHMS-KEOBGNEYSA-N
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 17090-79-8 | CASNo = 17090-79-8
| KEGG_Ref = {{keggcite|correct|kegg}}
| ATCvet = yes
| ATCCode_prefix = P51
| ATCCode_suffix = AH03
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D08228 | KEGG = D08228
| RTECS = | RTECS =
}} }}
| Section2 = {{Chembox Properties |Section2={{Chembox Properties
| Formula = C<sub>36</sub>H<sub>62</sub>O<sub>11</sub> | Formula = C<sub>36</sub>H<sub>62</sub>O<sub>11</sub>
| MolarMass = 670.871g/mol | MolarMass = 670.871&nbsp;g/mol
| Appearance = solid state, white crystals | Appearance = solid state, white crystals
| Density = | Density =
| Solubility = 3x10<sup>-6</sup> g/dm<sup>3</sup> (20 °C) | Solubility = 3x10<sup>−6</sup> g/dm<sup>3</sup> (20&nbsp;°C)
| Solvent = | Solvent =
| SolubleOther = ], ], ], ] | SolubleOther = ], ], ], ]
| MeltingPt = 104°C | MeltingPtC = 104
| BoilingPt = | MeltingPt_notes =
| Viscosity = | BoilingPt =
| RefractIndex = | Viscosity =
| RefractIndex =
}} }}
| Section8 = {{Chembox Related | Section6 = {{Chembox Pharmacology
| Function = | Pharmacology_ref =
| ATCCode_prefix = A16
| OtherFunctn = ], ]
| ATCCode_suffix = QA06
| OtherCpds = ],
| ATC_Supplemental = {{ATCvet|P51|BB03}}
}} }}
| ATCvet = yes
'''Monensin''', isolated from ''] cinnamonensis'', is a well-known representative of naturally ] ] ].
| Licence_EU =
| INN =
| INN_EMA =
| Licence_US =
| Legal_status =
| Legal_AU =
| Legal_AU_comment =
| Legal_CA = Rx-only
| Legal_CA_comment = <ref>{{cite web | title=Health product highlights 2021: Annexes of products approved in 2021 | website=] | date=3 August 2022 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | access-date=25 March 2024}}</ref>
| Legal_NZ =
| Legal_NZ_comment =
| Legal_UK =
| Legal_UK_comment =
| Legal_US =
| Legal_US_comment =
| Legal_EU =
| Legal_EU_comment =
| Legal_UN =
| Legal_UN_comment =
| Pregnancy_category =
| Pregnancy_AU =
| Pregnancy_AU_comment =
| Dependence_liability =
| AdminRoutes =
| Bioavail =
| ProteinBound =
| Metabolism =
| Metabolites =
| OnsetOfAction =
| HalfLife =
| DurationOfAction =
| Excretion =
}}
|Section8={{Chembox Related
| OtherFunction_label =
| OtherFunction = ], ]
| OtherCompounds = ],
}}
}}
'''Monensin''' is a ] ] isolated from '']''.<ref name=BMRI2013>{{cite journal |author= Daniel Łowicki and Adam Huczyński|year= 2013|title= Structure and Antimicrobial Properties of Monensin A and Its Derivatives: Summary of the Achievements|journal= BioMed Research International|volume= 2013|pages=1–14|doi=10.1155/2013/742149|pmid= 23509771|pmc= 3586448|doi-access= free}}</ref> It is widely used in ruminant animal feeds.<ref name=BMRI2013/><ref>{{cite journal | doi = 10.1128/CMR.16.2.175-188.2003| pmid = 12692092| pmc = 153145| title = Antimicrobial Growth Promoters Used in Animal Feed: Effects of Less Well Known Antibiotics on Gram-Positive Bacteria| journal = Clinical Microbiology Reviews| volume = 16| issue = 2| pages = 175–188| year = 2003| last1 = Butaye| first1 = P.| last2 = Devriese| first2 = L. A.| last3 = Haesebrouck| first3 = F.}}</ref>


The structure of monensin was first described by Agtarap et al. in 1967, and was the first polyether antibiotic to have its structure elucidated in this way. The first ] of monensin was reported in 1979 by ] et al.<ref name="Nicolaou">{{cite book |title= Classics in Total Synthesis|last= Nicolaou|first= K. C.|author-link=K. C. Nicolaou |author2=E. J. Sorensen|year= 1996|publisher= VCH|location= Weinheim, Germany|isbn= 3-527-29284-5|pages=–187 |url=https://archive.org/details/classicstotalmet00kcni_087|url-access= limited}}</ref>
==History==
The structure of monensin was first described by Agtarap ''et al.'' in 1967, and was the first polyether antibiotic to have its structure elucidated in this way. The first ] of monensin was reported in 1979 by Kishi ''et al.''<ref name="Nicolaou">{{cite book |title= Classics in Total Synthesis|last= Nicolaou|first= K. C.|authorlink=K. C. Nicolaou |coauthors= E. J. Sorensen|year= 1996|publisher= VCH|location= Weinheim, Germany|isbn= 3-527-29284-5|page= |pages=185–187 |url= |accessdate= }}</ref>


==Mechanism of action== ==Mechanism of action==
]
Monensin A exhibits significant preference to form complexes with monovalent ]s such as: Li<sup>+</sup>, Na<sup>+</sup>, K<sup>+</sup>, Rb<sup>+</sup>, Ag<sup>+</sup> and Tl<sup>+</sup> <ref> A. Huczyński, M. Ratajczak-Sitarz, A. Katrusiak, B. Brzezinski, ”Molecular structure of the 1:1 inclusion complex of Monensin A lithium salt with acetonitrile”, ''J. Mol. Struct.'', 2007, 871, 92-97, {{doi|10.1016/j.molstruc.2006.07.046}}</ref><ref>A. Huczyński, M. Ratajczak-Sitarz, A. Katrusiak, B. Brzezinski ”Molecular structure of the 1:1 inclusion complex of Monensin A sodium salt with acetonitrile” ''J. Mol. Struct.'', 2007, 832, 84-89, {{doi|10.1016/j.molstruc.2006.07.043}}</ref><ref>A. Huczyński, M. Ratajczak-Sitarz, A. Katrusiak, B. Brzezinski, "Molecular structure of rubidium six-coordinated dihydrate complex with monensin A", ''J. Mol. Struct.''{{doi|10.1016/j.molstruc.2007.12.005}}</ref><ref> M. Pinkerton, L. K. Steinrauf, "Molecular structure of monovalent metal cation complexes of monensin", ''J. Mol. Biol.'', 1970 49(3), 533-546</ref>. Monensin A is able to transport these cations across lipid membranes of cells, playing an important role as an Na<sup>+</sup>/H<sup>+</sup> ]. It blocks ] protein transport, and exhibits ], ], and other biological activities <ref>H. H. Mollenhauer, D. J. Morre, L. D. Rowe, ”Alteration of intracellular traffic by monensin; mechanism, specificity and relationship to toxicity”, ''Biochim. Biophys. Acta'', 1990, 1031(2), 225-246, {{doi|10.1016/0304-4157(90)90008-Z}}</ref>. The ] properties of monensin and its derivatives are a result of their ability to transport metal cations through cellular and subcellular ] <ref>A. Huczyński, J. Stefańska, P. Przybylski, B. Brzezinski and F. Bartl, "Synthesis and antimicrobial properties of Monensin A esters", ''Bioorganic & Medicinal Chemistry Letters'', 2008, 18, 2585-2589, {{doi|10.1016/j.bmcl.2008.03.038}}</ref><ref>A. Huczyński, P. Przybylski, B. Brzezinski, F. Bartl, ”Spectroscopic and semiempirical studies of a proton channel formed by the methyl ester of Monensin A”, ''J. Phys. Chem. B'', 2006, 110, 15615-15623, {{doi|10.1021/jp062160o}}</ref><ref>A. Huczyński, A. Domańska, I. Paluch, J. Stefańska, B. Brzezinski, F. Bartl, "Synthesis of new semi-synthetic dipodands and tripodands from naturally occurring polyether ionophores", ''Tetrahedron Letters'', 2008, 49(39), 5572-5575 {{doi|10.1016/j.tetlet.2008.06.116}} </ref>.
Monensin A is an ] related to the ]s with a preference to form complexes with monovalent ]s such as: Li<sup>+</sup>, Na<sup>+</sup>, K<sup>+</sup>, Rb<sup>+</sup>, Ag<sup>+</sup>, and Tl<sup>+</sup>.<ref>{{cite journal | last1 = Huczyński | first1 = A. | author-link4 = Bogumił Brzezinski | last2 = Ratajczak-Sitarz | first2 = M. | last3 = Katrusiak | first3 = A. | last4 = Brzezinski | first4 = B. | year = 2007 | title = Molecular structure of the 1:1 inclusion complex of Monensin A lithium salt with acetonitrile | journal = ] | volume = 871 | issue = 1–3| pages = 92–97 | doi = 10.1016/j.molstruc.2006.07.046 | bibcode = 2007JMoSt.871...92H }}</ref><ref>{{cite journal | last1 = Pinkerton | first1 = M. | last2 = Steinrauf | first2 = L. K. | year = 1970 | title = Molecular structure of monovalent metal cation complexes of monensin | journal = ] | volume = 49 | issue = 3| pages = 533–546 | doi=10.1016/0022-2836(70)90279-2| pmid = 5453344 }}</ref> Monensin A is able to transport these cations across lipid membranes of cells in an electroneutral (i.e. non-depolarizing) exchange, playing an important role as an Na<sup>+</sup>/H<sup>+</sup> ]. Recent studies have shown that monensin may transport sodium ion through the membrane in both electrogenic and electroneutral manner.<ref>{{cite journal|last=Huczyński|first=Adam|author2=Jan Janczak |author3=Daniel Łowicki |author4=Bogumil Brzezinski |title=Monensin A acid complexes as a model of electrogenic transport of sodium cation|journal= Biochimica et Biophysica Acta (BBA) - Biomembranes|date=2012|volume=1818|issue=9|pages=2108–2119|doi=10.1016/j.bbamem.2012.04.017|pmid=22564680|doi-access=free}}</ref> This approach explains ionophoric ability and in consequence antibacterial properties of not only parental monensin, but also its derivatives that do not possess carboxylic groups. It blocks ] protein transport, and exhibits ], ], and other biological activities.<ref>{{cite journal | last1 = Mollenhauer | first1 = H. H. | last2 = Morre | first2 = D. J. | last3 = Rowe | first3 = L. D. | year = 1990 | title = Alteration of intracellular traffic by monensin; mechanism, specificity and relationship to toxicity | journal = Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes| volume = 1031 | issue = 2| pages = 225–246 | doi = 10.1016/0304-4157(90)90008-Z | pmid = 2160275 | pmc = 7148783 }}</ref> The ] properties of monensin and its derivatives are a result of their ability to transport metal cations through cellular and subcellular ].<ref>{{cite journal | last1 = Huczyński | first1 = A. | last2 = Stefańska | first2 = J. | last3 = Przybylski | first3 = P. | last4 = Brzezinski | first4 = B. | last5 = Bartl | first5 = F. | year = 2008 | title = Synthesis and antimicrobial properties of Monensin A esters | journal = ] | volume = 18 | issue = 8| pages = 2585–2589 | doi = 10.1016/j.bmcl.2008.03.038 | pmid = 18375122 }}</ref>
]

{{-}}
==Uses== ==Uses==
Monensin is used extensively in the beef and dairy industries to prevent ], increase the production of propionic acid and prevent bloat.<ref>{{cite journal | last1 = Matsuoka | first1 = T. | last2 = Novilla | first2 = M.N. | last3 = Thomson | first3 = T.D. | last4 = Donoho | first4 = A.L. | year = 1996 | title = Review of monensin toxicosis in horses | journal = ] | volume = 16 | pages = 8–15 | doi = 10.1016/S0737-0806(96)80059-1 }}</ref> Furthermore, monensin, but also its derivatives monensin methyl ] (MME), and particularly monensin decyl ester (MDE) are widely used in ]s.<ref>{{cite journal | doi = 10.2116/analsci.6.227| title = A sodium ion selective electrode based on a highly lipophilic monensin derivative and its application to the measurement of sodium ion concentrations in serum| journal = Analytical Sciences| volume = 6| issue = 2| pages = 227–232| year = 1990| last1 = Tohda| first1 = Koji| last2 = Suzuki| first2 = Koji| last3 = Kosuge| first3 = Nobutaka| last4 = Nagashima| first4 = Hitoshi| last5 = Watanabe| first5 = Kazuhiko| last6 = Inoue| first6 = Hidenari| last7 = Shirai| first7 = Tsuneo| doi-access = free}}</ref><ref>{{cite journal | last1 = Kim | first1 = N. | last2 = Park | first2 = K. | last3 = Park | first3 = I. | last4 = Cho | first4 = Y. | last5 = Bae | first5 = Y. | year = 2005 | title = Application of a taste evaluation system to the monitoring of Kimchi fermentation | journal = ] | volume = 20 | issue = 11| pages = 2283–2291 | doi = 10.1016/j.bios.2004.10.007 | pmid = 15797327 }}</ref><ref>{{cite journal | last1 = Toko | first1 = K. | year = 2000 | title = Taste Sensor | journal = ] | volume = 64 | issue = 1–3| pages = 205–215 | doi = 10.1016/S0925-4005(99)00508-0 | bibcode = 2000SeAcB..64..205T }}</ref> In laboratory research, monensin is used extensively to block ] transport.<ref>{{Cite journal|last1=Griffiths|first1=G.|last2=Quinn|first2=P.|last3=Warren|first3=G.|date=March 1983|title=Dissection of the Golgi complex. I. Monensin inhibits the transport of viral membrane proteins from medial to trans Golgi cisternae in baby hamster kidney cells infected with Semliki Forest virus|journal=The Journal of Cell Biology|volume=96|issue=3|pages=835–850|issn=0021-9525|pmc=2112386|pmid=6682112|doi=10.1083/jcb.96.3.835}}</ref><ref>{{Cite journal|last1=Kallen|first1=K. J.|last2=Quinn|first2=P.|last3=Allan|first3=D.|date=1993-02-24|title=Monensin inhibits synthesis of plasma membrane sphingomyelin by blocking transport of ceramide through the Golgi: evidence for two sites of sphingomyelin synthesis in BHK cells|journal=Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism|volume=1166|issue=2–3|pages=305–308|issn=0006-3002|pmid=8443249|doi=10.1016/0005-2760(93)90111-l}}</ref><ref>{{Cite journal|last1=Zhang|first1=G. F.|last2=Driouich|first2=A.|last3=Staehelin|first3=L. A.|date=December 1996|title=Monensin-induced redistribution of enzymes and products from Golgi stacks to swollen vesicles in plant cells|journal=European Journal of Cell Biology|volume=71|issue=4|pages=332–340|issn=0171-9335|pmid=8980903}}</ref>
Monensin is used extensively in the beef and dairy industries to prevent coccidiosis, increase the production of propionic acid and prevent bloat.<ref> T. Matsuoka, M.N. Novilla, T.D. Thomson and A.L. Donoho, "Review of monensin toxicosis in horses", ''J. Equine Veterinary Science,'' 16, 1996, 8-15, {{doi|10.1016/S0737-0806(96)80059-1}}</ref>. Furthermore monensin, but also its derivatives monensin methyl ] (MME), and particularly monensin decyl ester (MDE) are widely used in ]s <ref>

K. Tohda, K. Suzuki, N. Kosuge, H. Nagashima, H. Inoue K. Watanabe, ”A Sodium Ion Selective Electrode Based on a Highly Lipophilic Monensin Derivative and Its Application to the Measurement of Sodium Ion Concentrations in Serum”, ''Analytical Sciences,'' 6, 1990, 227-232, {{doi|10.2116/analsci.6.227}}</ref><ref>
==Toxicity==
N. Kim, K. Park, I. Park, Y. Cho, Y. Bae, ”Application of a taste evaluation system to the monitoring of Kimchi fermentation”, ''Biosensors and Bioelectronics,'' 20, 2005, 2283-2291,{{doi|10.1016/j.bios.2004.10.007}}</ref><ref>
Monensin has some degree of activity on mammalian cells and thus toxicity is common. This is especially pronounced in horses, where monensin has a ] 1/100 that of ruminants. Accidental poisoning of equines with monensin is a well-documented occurrence which has resulted in deaths.<ref>{{Cite web |author=Jennifer Kay|url=https://apnews.com/511458b115b6487fbcfff0c8d1f45cb5 | title=Tainted feed blamed for 4 horse deaths at Florida stable| website=]| date=2014-12-16}}</ref> <ref>{{Cite web |author=Lacy Vilhauer|url=https://hpj.com/2024/08/27/nearly-70-horses-die-after-eating-feed-containing-monensin/?fbclid=IwY2xjawE-BYhleHRuA2FlbQIxMAABHYLdPgHXPGzY5uwwj9QJD7bcAv0k-UURJiDg9ADc-QahyzvxSThBNljWlg_aem_Akhr43ggBduKuWpiQ3imXQ | title=Nearly 70 horses die after eating feed containing monensin| website=]| date=2024-08-27}}</ref>
K. Toko, ”Taste Sensor”, ''Sensors and Actuators B: Chemical,'' 64, 2000, 205-215, {{doi|10.1016/S0925-4005(99)00508-0}}</ref>.


==References== ==References==
{{reflist}} {{reflist}}
{{Nonribosomally synthesized porters}} {{Nonribosomally synthesized porters}}

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