View source for Ajoene

{{Chembox
| verifiedrevid = 453573796
| ImageFile = Ajoene.svg
| ImageSize = 200px
| ImageAlt =
| ImageFile1 = (S,E)-ajoene-from-xtal-3D-bs-17.png
| PIN = (1''E'')-3-(Prop-2-ene-1-sulfinyl)-1-[(prop-2-en-1-yl)disulfanyl]prop-1-ene
| OtherNames =
|Section1={{Chembox Identifiers
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 122890
| CASNo_Ref = {{cascite|correct|??}}
| CASNo = 92285-01-3
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 99A0041VG8
| PubChem = 5386591
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4533332
| SMILES = O=S(C/C=C/SSC/C=C)C\C=C
| InChI = 1/C9H14OS3/c1-3-6-11-12-7-5-9-13(10)8-4-2/h3-5,7H,1-2,6,8-9H2/b7-5+
| InChIKey = IXELFRRANAOWSF-FNORWQNLBE
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C9H14OS3/c1-3-6-11-12-7-5-9-13(10)8-4-2/h3-5,7H,1-2,6,8-9H2/b7-5+
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IXELFRRANAOWSF-FNORWQNLSA-N
}}
|Section2={{Chembox Properties
| Formula = 
| C=9 | H=14 | O=1 | S=3
| Appearance =
| Density =
| MeltingPt =
| BoilingPt =
| Solubility = }}
|Section3={{Chembox Hazards
| MainHazards =
| FlashPt =
| AutoignitionPt = }}
}}

'''Ajoene''' {{IPAc-en|ˈ|ɑː|h|oʊ|.|iː|n}} is an [[organosulfur compound]] found in [[garlic]] (''Allium sativum'') extracts. It is a colorless liquid that contains [[sulfoxide]] and [[disulfide]] functional groups. The name<ref name="Block 1984">{{cite journal | doi=10.1021/ja00338a049| year=1984|vauthors=Block E, Ahmad S, Jain MK, Crecely R, Apitz-Castro R, Cruz MR |title=(''E'',''Z'')-Ajoene: A potent antithrombotic agent from garlic|journal=[[Journal of the American Chemical Society]]|volume=106| issue=26|pages=8295–8296}}</ref> (and pronunciation) is derived from "ajo", the [[Spanish language|Spanish]] word for garlic. It is found as a mixture of up to four [[stereoisomers]], which differ in terms of the stereochemistry of the central alkene (''E''- vs ''Z''-) and the chirality of the sulfoxide sulfur (''R''- vs ''S''-).

==History and syntheses==
The structure of ajoene was determined and it was synthesized based on biosynthetic considerations in 1984,<ref name="Block 1984" /> correcting an incorrect structure published in 1983.<ref>{{cite journal|last=Apitz-Cȧstro|first=R.|author2=Cabrera, S.|author3= Cruz, M.R.|author4= Ledezma, E.|author5= Jain, M.K.|title=Effects of garlic extract and of three pure components isolated from it on human platelet aggregation, arachidonate metabolism, release reaction and platelet ultrastructure|journal=[[Thrombosis Research]]|date= 1983|volume=32|issue=2|pages=155–169|doi=10.1016/0049-3848(83)90027-0|pmid=6419374 }}</ref> A short, scalable total synthesis of ajoene was reported in 2018 by Wirth and coworkers<ref name="Wirth 2018">{{cite journal|last=Silva|first=F.|author2=Khokhar, S.S.|author3= Williams, D.M.|author4= Saunders, R.|author5= Evans, G.J.S.|author6= Graz, M.|author7= Wirth, T. |title=Short total synthesis of ajoene|journal=[[Angewandte Chemie International Edition]]|date=2018|volume=57|issue=38|pages=12290–12293|doi=10.1002/anie.201808605|pmid=30079981|pmc=6221122|url=http://orca.cf.ac.uk/114186/8/Silva_et_al-2018-Angewandte_Chemie_International_Edition%20FINAL%20%28002%29.pdf}}</ref> while a biosynthetically modeled synthesis of trifluoroajoene from difluoroallicin was published in 2017.<ref>{{cite journal|last=Block|first=E.|author2=Bechand, B.|author3= Gundala, S.|author4= Vattekkatte, A.|author5= Wang, K.|author6= Mousa, Shaymaa|author7= Godugu, K. |author8= Yalcin, M.|author9= Mousa, Shaker|title=Fluorinated analogs of organosulfur compounds from garlic (''Allium sativum''). Synthesis, chemistry and anti-angiogenesis and antithrombotic studies.|journal=[[Molecules]]|date=2017|volume=22|issue=12|pages=2081|doi=10.3390/molecules22122081|pmid=29182588|pmc=6149718 |doi-access=free }}</ref> Syntheses of various ajoene analogues have also been reported.<ref name="Kaschula 2012">{{cite journal |author=Kaschula CH |title= Structure-activity studies on the anti-proliferation activity of ajoene analogues in WHCO1 oesophageal cancer cells | journal=European Journal of Medicinal Chemistry |volume= 50 | year=2012 | pages=236–254 | pmid=22381354 |doi=10.1016/j.ejmech.2012.01.058 |display-authors=etal}}</ref> The chemistry of ajoene has been extensively investigated.<ref name="Block 1984" /><ref>{{cite journal | author=Block, E | title= The chemistry of garlic and onions | journal=[[Scientific American]] | volume=252 | issue= 3| year=1985 | pages=114–119 | doi=10.1038/scientificamerican0385-114 | pmid = 3975593 | bibcode= 1985SciAm.252c.114B }}</ref><ref>{{cite journal|last=Apitz-Castro|first=R|author2=Escalante, J|author3= Vargas, R|author4= Jain, MK|title=Ajoene, the antiplatelet principle of garlic, synergistically potentiates the antiaggregatory action of prostacyclin, forskolin, indomethacin and dypiridamole on human platelets.|journal=Thrombosis Research|date= 1986|volume=42|issue=3|pages=303–11|pmid=3520940|doi=10.1016/0049-3848(86)90259-8}}</ref><ref>{{cite journal | doi=10.1021/ja00282a033| year=1986|vauthors=Block E, Ahmad S, Catalfamo JL, Jain MK, Apitz-Castro R |title=The chemistry of alkyl thiosulfinate esters. 9. Antithrombotic organosulfur compounds from garlic: structural, mechanistic, and synthetic studies|journal=Journal of the American Chemical Society|volume=108| issue=22|pages=7045–7055}}</ref><ref name="Block 2010">{{cite book | author=Block, E | title=Garlic and Other Alliums: The Lore and the Science | publisher=[[Royal Society of Chemistry]] | year=2010 | isbn=978-0-85404-190-9}}</ref>

When a garlic clove is crushed or finely chopped, allicin is released, with subsequent formation of ajoene when the material is dissolved in various solvents including [[edible oil]]s. Ajoene is also found in garlic extract. Ajoene is most stable and most abundant in macerate of garlic (chopped garlic in edible oil).

The reaction sequence that forms ajoene ('''2''' in the diagram) involves two molecules of allicin. First, one allicin molecule ('''1''' in the diagram) fragments to form 2-propenesulfenic acid and thio[[acrolein]]. These two react in separate stages with another allicin molecule by way of a conjugated thiocationic intermediate.<ref name="Block 1984" />

[[File:Mechanism_for_formation_of_ajoene_from_allicin.tiff|600px|]]

==Medicinal properties==
Ajoene has multiple [[medicine|medicinal uses]].<ref name="Wirth 2018"  /><ref name="Kaschula 2012"  /><ref name="Block 2010"  /> It functions as an [[antioxidant]] by inhibiting the release of [[superoxide]]. Ajoene also has antithrombotic (anti-clotting) properties, which helps prevent [[platelet]]s in the [[blood]] from forming [[blood clot]]s, potentially reducing the risk of [[heart disease]] and [[stroke]] in humans. Ajoene has shown potential virucidal properties against a number of viruses including vesicular stomatitis, vaccinia, human rhinovirus parainfluenza, and herpes simplex. In the infected cell system of a human immunodeficiency virus (HIV), it is shown to block the [[integrin]]-dependent processes.<ref>{{cite journal |vauthors=Weber ND, Andersen DO, North JA |title= In vitro virucidal effects of ''Allium sativum'' (garlic) extract and compounds | journal=Planta Med | volume=58 | issue=5 | year=1992 | pages=417–23 | pmid=1470664 | doi=10.1055/s-2006-961504|s2cid= 260284188 |display-authors=etal}}</ref><ref>{{cite journal |vauthors=Tatarintsev AV, Vrzhets PV, Ershov DE |title= The ajoene blockade of integrin-dependent processes in an HIV-infected cell system | journal=Vestn Ross Akad Med Nauk | year=1992 | pages=6–10 | pmid=1284227 | issue=11–12|display-authors=etal}}</ref>

Ajoene has broad-spectrum antimicrobial (antibacterial and antifungal) properties.<ref>{{cite journal |vauthors=Torres J, Romero H | title= In vitro antifungal activity of ajoene on five clinical isolates of ''Histoplasma capsulatum'' var. capsulatum | journal=Revista Iberoamericana de Micologia | volume=29 | issue=1 | year=2012 | pages=24–28 | pmid = 21635962 | doi=10.1016/j.riam.2011.04.001}}</ref><ref name=":0">{{cite journal |vauthors=Ledezma E, Apitz-Castro R | title= Ajoene the main active compound of garlic (''Allium sativum''): a new antifungal agent | journal=Revista Iberoamericana de Micologia | volume=23 | issue=2 | year=2006 | pages=75–80 | pmid=16854181 | doi=10.1016/s1130-1406(06)70017-1}}</ref><ref>{{cite journal | author= Choi JA | title= Enhancement of the antimycobacterial activity of macrophages by ajoene. | journal=Innate Immunity | year=2018 | doi=10.1177/1753425917747975 | pmid = 29239661 | volume=24 | issue= 1| pages=79–88| pmc= 6830758 |display-authors=etal| doi-access=free }}</ref> For example, Ajoene has been shown to have activity against the human dermatophyte ''Trichophyton rubrum'', the most common cause of tinea pedis, commonly known as Athlete's Foot.<ref name=":0" /><ref name=":1" /> The specific mechanism of action is unclear, but is thought to be related to the inhibition of phosphatidylcholine biosynthesis in human dermatophytes.<ref name=":1" /> In a randomized study by Ledezma et al. (2000), 70 soldiers from the Venezuelan Armed Forces with KOH or culture proven tinea pedis interdigitalis were randomly distributed into 3 treatment groups: 0.6% ajoene, 1% ajoene, and 1% terbinafine (commercially available as Lamisil AT®) applied twice daily for 1 week.<ref name=":1">{{Cite journal|last1=Ledezma|first1=E.|last2=Marcano|first2=K.|last3=Jorquera|first3=A.|last4=De Sousa L|first4=L.|last5=Padilla|first5=M.|last6=Pulgar|first6=M.|last7=Apitz-Castro|first7=R.|date=2000|title=Efficacy of ajoene in the treatment of tinea pedis: a double-blind and comparative study with terbinafine|journal=Journal of the American Academy of Dermatology|volume=43|issue=5 Pt 1|pages=829–832|issn=0190-9622|pmid=11050588|doi=10.1067/mjd.2000.107243}}</ref> At the 60 day follow up, 72%, 100%, and 94% of the patients treated with 0.6% and 1% ajoene, and 1% terbinafine, respectively, had maintained culture-proven mycologic cure suggesting that short-term topical treatment with ajoene is at least as effective as topical terbinafine for treating tinea pedis.<ref name=":1" />

Ajoene has been investigated as a chemotherapeutic agent for treatment of [[cancer stem cells]] in [[glioblastoma multiforme]],<ref>{{cite journal |vauthors= Jung Y, Park H, Zhao HY, Jeon R, Ryu JH, Kim WY | title= Systemic approaches identify a garlic-derived chemical, Z-ajoene, as a glioblastoma multiforme cancer stem cell-specific targeting agent | journal=Molecules and Cells | volume=37 | issue=7 | year=2014 | pages=547–553 | pmid = 25078449 | pmc= 4132307 | doi=10.14348/molcells.2014.0158}}</ref> of [[lung adenocarcinoma]]<ref>{{cite journal |vauthors= Wang Y, Sun Z, Chen S, Jiao Y, Bai C | title= ROS-mediated activation of JNK/p38 contributes partially to the pro-apoptotic effect of ajoene on cells of lung adenocarcinoma | journal=Tumour Biology | volume=37 | issue=3 | year=2016 | pages=3727–3738 | pmid = 26468015 | doi=10.1007/s13277-015-4181-9| s2cid= 10601109 }}</ref> and as an anti-leukemia agent for [[acute myeloid leukemia]] therapy.<ref>{{cite journal | author=Hassan HT | title= Ajoene (natural garlic compound): a new anti-leukaemia agent for AML therapy | journal=Leukemia Research| volume=28 | issue=7 | year=2004 | pages=667–671 | pmid = 15158086 | doi=10.1016/j.leukres.2003.10.008}}</ref> Ajoene has been found to decrease [[basal-cell carcinoma]] tumor size by inducing apoptosis<ref>{{cite journal |author1=Tilli CMLJ |author2=Stavast-Kooy AJW |author3=Vuerstaek JDD | title= The garlic-derived organosulfur component ajoene decreases basal cell carcinoma tumor size by inducing apoptosis| journal=Archives of Dermatological Research| volume=295 | issue=3 | year=2003 | pages=117–123 | pmid=12756587| doi=10.1007/s00403-003-0404-9|s2cid=23299332 |display-authors=etal}}</ref> while it has also been shown effective in inhibiting [[tumor]] [[Cell (biology)|cell]] growth by targeting the [[microtubule]] cytoskeleton of such cells and by other mechanisms.<ref>{{cite journal |vauthors=Terrasson J, Xu B, Li M, Allart S, Davignon JL, Zhang LH, Wang K, Davrinche C | title= Activities of ''Z''-ajoene against tumour and viral spreading in vitro | journal=Fundamental & Clinical Pharmacology | volume=21 | issue=3 | year=2007 | pages=281–289 | pmid = 17521297 | doi=10.1111/j.1472-8206.2007.00470.x| doi-access=free }}</ref> Ajoene inhibits genes controlled by [[quorum sensing]],<ref name="Wirth 2018"  /><ref>{{cite journal | author=Givskov M | title= Ajoene, a sulfur rich molecule from garlic, inhibits genes controlled by quorum sensing | journal=[[Antimicrobial Agents and Chemotherapy]] | year=2012 | doi=10.1128/AAC.05919-11 | pmid = 22314537 | pmc= 3346669 | volume=56 | issue=5 | pages=2314–25|display-authors=etal| url=http://www.zora.uzh.ch/59241/1/Jakobsen_et_al_Ajoene.pdf }}</ref><ref>{{cite journal | author= Jakobsen TH | title= A broad range quorum sensing inhibitor working through sRNA inhibition | journal=[[Scientific Reports]] | year=2017 | doi=10.1038/s41598-017-09886-8 | pmid = 28851971 | pmc= 5575346 | volume=7 | issue= 1| pages=9857| bibcode= 2017NatSR...7.9857J |display-authors=etal}}</ref> through binding to the RNA chaperone Hfq, then hindering its interaction with the small RNAs that, ultimately, control the production of quorum sensing autoinducers.<ref>{{cite journal | doi=10.1128/AAC.05919-11 | pmid =  22314537 | year=2010|vauthors=Jakobsen TH, van Gennip M, Phipps RK, Shanmugham MS, Christensen LD, Alhede M, Skindersoe ME, Rasmussen TB, Friedrich K, Uthe F, Jensen PØ, Moser C, Nielsen KF, Eberl L, Larsen TO, Tanner D, Høiby N, Bjarnsholt T, Givskov M |title= Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by Quorum Sensing|journal=[[Antimicrobial Agents and Chemotherapy]]|volume=56| issue=5|pages=2314-2325|pmc=3346669}}</ref> Since this interaction occurs at the proximal Hfq binding site (the first site that small RNAs bind to), the subsequent pairing with  messenger RNAs never occurs and the expression of virulence factors in Gram-negatives is impaired.<ref>{{cite journal | doi=10.1016/j.gene.2023.147506| pmid =  37224934 | year=2023 | vauthors=Fiori-Duarte AT, Sousa-Ferreira LB, Ascencio AS, Kawano DF |title= Modulation of Pseudomonas aeruginosa quorum sensing by ajoene through direct competition with small RNAs for binding at the proximal site of Hfq – A structure-based perspective|journal=[[Gene]]|volume=877| issue=1|pages=147506.}}</ref>

==References==
{{reflist|2}}

==External links==
{{commons category inline|Ajoene}}

[[Category:Organic disulfides]]