CoChat
Sign Up
Cited by 217Garlic and Onion StudiesAntimicrobial agents and applicationsEssential Oils and Antimicrobial Activity

A Comparison of the Antibacterial and Antifungal Activities of Thiosulfinate Analogues of Allicin

Open access
Leontiev, Roman, Hohaus, Nils, Jacob, Claus, Gruhlke, Martin C. H., Slusarenko, Alan J.·2018·Scientific Reports
DOI 10.1038/s41598-018-25154-9PMC PMC5928221
Open this paper in CoChat — free accountOpen PDF

Abstract

Allicin (diallylthiosulfinate) is a defence molecule from garlic ( Allium sativum L.) with broad antimicrobial activities in the low µM range against Gram-positive and -negative bacteria, including antibiotic resistant strains, and fungi. Allicin reacts with thiol groups and can inactivate essential enzymes. However, allicin is unstable at room temperature and antimicrobial activity is lost within minutes upon heating to >80 °C. Allicin’s antimicrobial activity is due to the thiosulfinate group, so we synthesized a series of allicin analogues and tested their antimicrobial properties and thermal stability. Dimethyl-, diethyl-, diallyl-, dipropyl- and dibenzyl-thiosulfinates were synthesized and tested in vitro against bacteria and the model fungus Saccharomyces cerevisiae , human and plant cells in culture and Arabidopsis root growth. The more volatile compounds showed significant antimicrobial properties via the gas phase. A chemogenetic screen with selected yeast mutants showed that the mode of action of the analogues was similar to that of allicin and that the glutathione pool and glutathione metabolism were of central importance for resistance against them. Thiosulfinates differed in their effectivity against specific organisms and some were thermally more stable than allicin. These analogues could be suitable for applications in medicine and agriculture either singly or in combination with other antimicrobials.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41598-018-25154-9

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Garlic organosulfur compounds such as allicin, thiosulfinates, and ajoene act as antibacterial agents.

    “Experiments with separated compounds showed that fructans work as prebiotics for the gut microbiome [22] while garlic OSCs, such as allicin, thiosulfinates, and ajoene, act as antibacterial agents [23,24].”

    From Preventive Effects and Mechanisms of Garlic on Dyslipidemia and Gut Microbiome Dysbiosis (2019) · cites this paper as [23]

    The Introduction identifies allicin as fresh garlic’s main antibacterial compound and reports antimicrobial activity for thiosulfinates; the Results and Discussion also describe antibacterial effects of the thiosulfinates tested. Our copy does not report antibacterial activity for ajoene: it appears only in a reference concerning cholesterol biosynthesis. No page numbers are provided in the indexed passages. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 56 · Cited by 217

Research works printed but not linked: 46

  1. [2]Harris JC Cottrell S Plummer S Lloyd D Antimicrobial properties of Allium sativum (garlic) Applied Microbiology and Biotechnology 2001 57 282 286 10.1007/s002530100722 11759674 · DOI
  2. [4]Abramovitz D Allicin-induced decrease in formation of fatty streaks (atherosclerosis) in mice fed a cholesterol-rich diet Coron. Artery Dis. 1999 10 515 519 10.1097/00019501-199910000-00012 10562920 · DOI
  3. [5]Eilat S Alteration of lipid profile in hyperlipidemic rabbits by allicin, an active constituent of garlic Coron. Artery Dis. 1995 6 985 990 8723021
  4. [6]Gebhardt R Beck H Wagner KG Inhibition of cholesterol biosynthesis by allicin and ajoene in rat hepatocytes and HepG2 cells Biochim. Biophys. Acta (BBA) 1994 1213 57 62 10.1016/0005-2760(94)90222-4 8011681 · DOI
  5. [8]Benavides GA Hydrogen sulfide mediates the vasoactivity of garlic Proc. Natl. Acad. Sci. 2007 104 17977 17982 10.1073/pnas.0705710104 17951430 PMC2084282 · DOI
  6. [9]Ried K Frank O Stocks N Fakler P Sullivan T Effect of garlic on blood pressure: A systematic review and meta-analysis BMC Cardiovasc. Dis. 2008 8 13 10.1186/1471-2261-8-13 PMC2442048 18554422 · DOI
  7. [10]Silagy C Neil H A meta-analysis of the effect of garlic on blood pressure J. Hypertens. 1995 12 463 468 8064171
  8. [11]Turner B Molgaard C Marckmann P Effect of garlic (Allium sativum) powder tablets on serum lipids, blood pressure and arterial stiffness in normo-lipidaemic volunteers: a randomised, double-blind, placebo-controlled trial Br. J. Nutr. 2004 92 701 706 10.1079/BJN20041255 15522140 · DOI
  9. [12]Chan JY Yuen AC Chan RY Chan SW A review of the cardiovascular benefits and antioxidant properties of allicin Phytother. Res. 2013 27 637 646 10.1002/ptr.4796 22888009 · DOI
  10. [13]Hirsch K Effect of purified allicin, the major ingredient of freshly crushed garlic, on cancer cell proliferation Nutrit. Cancer 2000 38 245 254 10.1207/S15327914NC382_14 11525603 · DOI
  11. [14]Siegers CP Steffen B Röbke A Pentz R The effects of garlic preparations against human tumor cell proliferation Phytomedicine 1999 6 7 11 10.1016/S0944-7113(99)80028-2 10228605 · DOI
  12. [15]Cavallito CJ Bailey JH Allicin, the Antibacterial Principle of Allium sativum I. Isolation, Physical Properties and Antibacterial Action J. Am. Chem. Soc. 1944 66 1950 1951 10.1021/ja01239a048 · DOI
  13. [16]Cavallito CJ Buck JS Suter CM Allicin, the Antibacterial Principle of Allium sativum. II. Determination of the Chemical Structure J. Am. Chem. Soc. 1944 66 1952 1954 10.1021/ja01239a049 · DOI
  14. [17]Curtis H Noll U Störmann J Slusarenko AJ Broad-spectrum activity of the volatile phytoanticipin allicin in extracts of garlic (Allium sativum L.) against plant pathogenic bacteria, fungi and Oomycetes Physiol. Mol. Plant Pathol. 2004 65 79 89 10.1016/j.pmpp.2004.11.006 · DOI · Paper page
  15. [18]Fujisawa H Antibacterial Potential of Garlic-Derived Allicin and its Cancellation by Sulfhydryl Compounds Biosci. Biotechnol. Biochem. 2009 73 1948 1955 10.1271/bbb.90096 19734685 · DOI
  16. [20]Ankri S Mirelman D Antimicrobial properties of allicin from garlic Microbes Infect. 1999 1 125 129 10.1016/S1286-4579(99)80003-3 10594976 · DOI
  17. [21]Kubec R Musah RA Cysteine sulfoxide derivatives in Petiveria alliacea Phytochemistry 2001 58 981 5 10.1016/S0031-9422(01)00304-1 11684199 · DOI
  18. [22]Kim S Kubec R Musah RA Antibacterial and antifungal activity of sulfur-containing compounds from Petiveria alliacea L Journal of Ethnopharmacology 2006 104 188 192 10.1016/j.jep.2005.08.072 16229980 · DOI
  19. [23]Small LD Bailey JH Cavallito CJ Alkyl Thiolsulfinates Journal of the American Chemical Society 1947 69 1710 1713 10.1021/ja01199a040 20251406 · DOI
  20. [24]Hunter R Caira M Stellenboom N Thiolsulfinate Allicin from Garlic: Inspiration for a New Antimicrobial Agent Annals of the New York Academy of Sciences 2005 1056 234 241 10.1196/annals.1352.011 16387691 · DOI
  21. [25]Reiter J Diallylthiosulfinate (Allicin), a Volatile Antimicrobial from Garlic (Allium sativum), Kills Human Lung Pathogenic Bacteria, Including MDR Strains, as a Vapor Molecules 2017 22 1711 10.3390/molecules22101711 PMC6151386 29023413 · DOI
  22. [26]Wallock-Richards, D. et al. Garlic Revisited: Antimicrobial Activity of Allicin-Containing Garlic Extracts against Burkholderia cepacia Complex. 2014, PLoS ONE9(12) (2014). PMC4249831 25438250
  23. [27]Haase H Impact of allicin on macrophage activity Food Chem. 2012 134 141 148 10.1016/j.foodchem.2012.02.080 · DOI
  24. [31]Gruhlke MCH Slusarenko AJ The biology of reactive sulfur species (RSS) Plant Physiol. Biochem. 2012 59 98 107 10.1016/j.plaphy.2012.03.016 22541352 · DOI
  25. [32]Albrecht F Leontiev R Jacob C Slusarenko AJ An Optimized Facile Procedure to synthesize and purify Allicin Molecules 2017 22 770 10.3390/molecules22050770 PMC6154629 28489057 · DOI
  26. [33]Wills ED Enzyme Inhibition by Allicin, the Active Principle of Garlic Biochem. J. 1956 63 514 520 10.1042/bj0630514 13341914 PMC1216205 · DOI
  27. [34]Winkler G Iberl B Knobloch K Reactivity of Allicin and its Transformation Products with Sulfhydryl Groups, Disulfide Groups, and Human Blood Planta Med. 1992 58 665 10.1055/s-2006-961678 · DOI
  28. [35]Han J Modification of catalytic properties of chicken liver fructose 1,6-bisphosphatase by allicin Biochem. Mol. Biol. Intern. 1993 31 1007 1015 8193584
  29. [36]Müller A Allicin Induces Thiol Stress in Bacteria through S-Allylmercapto Modification of Protein Cysteines J. Biol. Chem. 2016 291 11477 11490 10.1074/jbc.M115.702308 27008862 PMC4882420 · DOI
  30. [37]Gruhlke MCH Allicin disrupts the cell’s electrochemical potential and induces apoptosis in yeast Free Radic. Biol. Med. 2010 49 1916 1924 10.1016/j.freeradbiomed.2010.09.019 20883774 · DOI
  31. [38]Gruhlke MCH Yap1p, the central regulator of the S. cerevisiae oxidative stress response, is activated by allicin, a natural oxidant and defence substance of garlic Free Radical Biology and Medicine 2017 108 793 802 10.1016/j.freeradbiomed.2017.05.004 28479370 · DOI
  32. [39]López-Mirabal HR Thorsen M Kielland-Brandt MC Toledano MB Winther JR Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4′-dipyridyl disulfide FEMS Yeast Research 2007 7 391 403 10.1111/j.1567-1364.2006.00202.x 17253982 · DOI
  33. [41]Gruhlke MCH The defense substance allicin from garlic permeabilizes membranes of Beta vulgaris, Rhoeo discolor, Chara corallina and artificial lipid bilayers Biochim. Biophys. Acta (BBA) 2015 1850 602 611 10.1016/j.bbagen.2014.11.020 25484312 · DOI
  34. [42]Fujisawa H Biological and Chemical Stability of Garlic-Derived Allicin Journal of Agricultural and Food Chemistry 2008 56 4229 4235 10.1021/jf8000907 18489116 · DOI
  35. [44]Waag T Allicin and derivates are cysteine protease inhibitors with antiparasitic activity Bioorg. Medic. Chem. Lett. 2010 20 5541 5543 10.1016/j.bmcl.2010.07.062 20692829 · DOI
  36. [45]Kyung KH Fleming HP S-Methyl-L-Cysteine Sulfoxide as the Precursor of Methyl Methanethiolsulfinate, the Principal Antibacterial Compound in Cabbage J. Food Sci. 1994 59 350 355 10.1111/j.1365-2621.1994.tb06964.x · DOI
  37. [46]Kyung KH Fleming HP Antimicrobial activity of sulfur compounds derived from cabbage J. Food Protect. 1997 60 67 71 10.4315/0362-028X-60.1.67 10465044 · DOI
  38. [48]Leontiev R Slusarenko AJ Finding the Starting Point for Mode-of-Action Studies of Novel Selenium Compounds: Yeast as a Genetic Toolkit Curr. Org. Synth. 2017 14 1 7 10.2174/1570179414666170329133045 · DOI
  39. [49]Morano KA Grant CM Moye-Rowley WS The response to heat shock and oxidative stress in Saccharomyces cerevisiae Genetics 2012 190 1157 1195 10.1534/genetics.111.128033 22209905 PMC3316637 · DOI
  40. [50]Smyth AR Garlic as an inhibitor of Pseudomonas aeruginosa quorum sensing in cystic fibrosis—A pilot randomized controlled trial Pediatr. Pulm. 2010 45 315 416 10.1002/ppul.21115 20306535 · DOI
  41. [51]Portz D Koch E Slusarenko AJ Effects of garlic (Allium sativum L.) juice containing allicin on Phytophthora infestans (Mont. de Bary) and on downy mildew of cucumber caused by Pseudoperonospora cubensis (Berk. & M. A. Curtis) Rostovzev European Journal of Plant Pathology 2008 122 197 206 10.1007/s10658-008-9334-x · DOI · Paper page
  42. [52]Slusarenko AJ Patel A Portz D Control of plant diseases by natural products: Allicin from garlic as a case study European Journal of Plant Pathology 2008 121 313 322 10.1007/s10658-007-9232-7 · DOI · Paper page
  43. [53]Nagata T Nemoto Y Hasezawa S Tobacco BY-2 cell line as the “HeLa” cell in the cell biology of higher plants International Review of Cytology 1992 132 1 30 10.1016/S0074-7696(08)62452-3 · DOI
  44. [54]Khare D Arabidopsis ABCG34 contributes to defense against necrotrophic pathogens by mediating the secretion of camalexin PNAS 2017 114 5712 5720 10.1073/pnas.1702259114 PMC5514727 28652324 · DOI
  45. [55]Parisy V Identification of PAD2 as a gamma-glutamylcysteine synthetase highlights the importance of glutathione in disease resistance of Arabidopsis Plant J. 2007 49 159 172 10.1111/j.1365-313X.2006.02938.x 17144898 · DOI
  46. [56]Mhamdi A Arabidopsis GLUTATHIONE REDUCTASE1 Plays a Crucial Role in Leaf Responses to Intracellular Hydrogen Peroxide and in Ensuring Appropriate Gene Expression through Both Salicylic Acid and Jasmonic Acid Signaling Pathways Plant Physiol. 2010 153 1144 1160 10.1104/pp.110.153767 20488891 PMC2899936 · DOI

Authors
Leontiev, R., Hohaus, N., Jacob, C., Gruhlke, M. C. H., & Slusarenko, A. J.
Affiliations
  • RWTH Aachen University (DE)
  • Saarland University (DE)
Corresponding author
Slusarenko, Alan J.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-04-30
Volume
8
Issue
1
Pages
6763-6763
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-25154-9
PMC
PMC5928221
OpenAlex
W2799343390
Cited by
217
References
56
Citations by year
2026: 15 · 2025: 26 · 2024: 26 · 2023: 36 · 2022: 30 · 2021: 34 · 2020: 26 · 2019: 21 · 2018: 3
FWCI
20.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
Funders
RWTH Aachen University
Topics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Garlic and Onion Studies
  • Physical Sciences › Chemistry › Organic Chemistry › Antimicrobial agents and applications
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Essential Oils and Antimicrobial Activity
Keywords
allicin, thiosulfinates, antibacterial activity, antifungal activity, Saccharomyces cerevisiae, thermal stability, glutathione metabolism, thiol reactivity, antibiotic resistance
MeSH terms
Anti-Bacterial Agents, Antifungal Agents, Bacteria, Disulfides, Fungi, Garlic, Glutathione, Humans, Plant Extracts, Saccharomyces cerevisiae, Sulfhydryl Compounds, Sulfinic Acids, Thiosulfonic Acids, Arabidopsis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review