Synthesis and Antimicrobial Activity of Thiosulfinates, Allicin Analogues

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Abstract

Diallyl thiosulfinate (allicin) effectively inhibits the growth of various microorganisms, including antibiotic-resistant strains, so it can be considered a broad-spectrum antimicrobial compound. However, its instability in the bloodstream hinders its use as a therapeutic agent. We have synthesized a number of allicin analogues, both natural and synthetic, and evaluated in vitro their antimicrobial properties against Staphylococcus aureus and Candida albicans. The synthesized compounds were shown to exhibited more pronounced antifungal activity than antibacterial one. Among the compounds obtained, synthetic di-(2,2,2-trichloroethyl) ester of 3,3'-[(thio)sulfinyl]dipropionic acid effectively inhibited the growth of both fungi and bacteria at concentrations comparable to those of known antimicrobial agents used in medical practice.

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About the authors

V. M. Puchkov

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: elmorozova@yahoo.com
Russian Federation, Moscow, 119991

A. D. Lyfenko

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: elmorozova@yahoo.com
Russian Federation, Moscow, 119991

V. S. Koval

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: elmorozova@yahoo.com
Russian Federation, Moscow, 119991

S. V. Revtovich

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: elmorozova@yahoo.com
Russian Federation, Moscow, 119991

V. V. Kulikova

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: elmorozova@yahoo.com
Russian Federation, Moscow, 119991

N. V. Anufrieva

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: elmorozova@yahoo.com
Russian Federation, Moscow, 119991

A. S. Zemskaya

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: elmorozova@yahoo.com
Russian Federation, Moscow, 119991

E. A. Morozova

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Author for correspondence.
Email: elmorozova@yahoo.com
Russian Federation, Moscow, 119991

P. N. Solyev

Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences

Email: elmorozova@yahoo.com
Russian Federation, Moscow, 119991

References

  1. Hall-Stoodley L., Costerton J.W., Stoodley P. (2004) Bacterial biofilms: from the natural environment to infectious diseases. Nat. Rev. Microbiol. 2, 95–108.
  2. Nobile C.J., Johnson A.D. (2015) Candida albicans biofilms and human disease. Annu. Rev. Microbiol. 69, 71–92.
  3. Wolcott R., Costerton J.W., Raoult D., Culter S.J. (2013) The polymicrobial nature of biofilm infection. Clin. Microbiol. Infect. 19, 107–112.
  4. Goetghebeur M., Landry P.A., Han D., Vicente C. (2007) Methicillin resistant Staphylococcus aureus: a public health issue with economic consequences. Can. J. Infect. Dis. Med. Microbiol. 18, 27–34.
  5. Silva-Santana G., Lenzi-Almeida K.C., Lopes V.G.S., Aguiar-Alves F. (2016) Biofilm formation in catheter-related infections by panton-valentine leukocidin-producing Staphylococcus aureus. Int. Microbiol. 19, 199–207.
  6. Peters B.M., Jabra-Rizk M.A., O’May G.A., Costerton J.W., Shirtliff M.E. (2012) Polymicrobial interactions in biofilms: impact on pathogenesis and human disease. Clin. Microbiol. Rev. 25, 193–213.
  7. Klotz S.A., Chasin B.S., Powell B., Gaur N.K., Lipke P.N. (2007) Polymicrobial bloodstream infections involving Candida species: analysis of patients and review of the literature. Diagn. Microbiol. Infect. Dis. 59, 401–406.
  8. Pfaller M.A., Diekema D.J. (2007) Epidemiology of invasive candidiasis: a persistent public health problem. Clin. Microbiol. Rev. 20, 133–163.
  9. Harriott M.M., Noverr M.C. (2010) Ability of Candida albicans mutants to induce Staphylococcus aureus vancomycin resistance during polymicrobial biofilm formation. Antimicrob. Agents Chemother. 54, 3746–3755.
  10. Lebeaux D., Ghigo J.M., Beloin C. (2014) Biofilm-related infections: bridging the gap between clinical management and fundamental aspects of recalcitrance toward antibiotics. Microbiol. Mol. Biol. Rev. 78, 510–543.
  11. Borlinghaus J., Albrecht F., Gruhlke M.C.H., Nwachukwu I.D., Slusarenko A.J. (2014) Allicin: chemistry and biological properties. Molecules. 19, 12591‒12618.
  12. Sharifi-Rad J., Hoseini Alfatemi S., Sharifi Rad M., Iriti M. (2014) Antimicrobial synergic effect of allicin and silver nanoparticles on skin infection caused by methicillin-resistant Staphylococcus aureus spp. Ann. Med. Health Sci. Res. 4(6), 863–868.
  13. Muller A., Eller J., Albrecht F., Prochnow P., Kuhlmann K., Bandow J.E., Slusarenko A.J., Leichert L.I.O. (2016) Allicin induces thiol stress in bacteria through S-allylmercapto modification of protein systeines. J. Biol. Chem. 291, 11477–11490.
  14. Leontiev R., Hohaus N., Jacob C., Gruhlke M.C.H., Slusarenko A.J. (2018) A comparison of the antibacterial and antifungal activities of thiosulfinate analogues of allicin. Sci. Rep. 8, 6763.
  15. Revtovich S., Morozova E., Kulikova V., Koval V., Anufrieva N., Nikulin A., Demidkina T. (2020) Sulfoxides of sulfur-containing amino acids are suicide substrates of Citrobacter freundii methionine γ-lyase. Structural bases of the enzyme inactivation. Biochimie. 168, 190–197.
  16. Anufrieva N.V., Morozova E.A., Kulikova V.V., Bazhulina N.P., Manukhov I.V., Degtev D.I., Gnuchikh E.Y., Rodionov A.N., Zavilgelsky G.B., Demidkina T.V. (2015) Sulfoxides, analogues of L-methionine and L-cysteine as pro-drugs against Gram-positive and Gram-negative bacteria. Acta Naturae. 7(27), 128–135.
  17. Revtovich S., Lyfenko A., Tkachev Y., Kulikova V., Koval V., Puchkov V., Anufrieva N., Solyev P., Morozova E. (2023) Anticandidal activity of in situ methionine γ-lyase-based thiosulfinate generation system vs. synthetic thiosulfinates. Pharmaceuticals. 16(12), 1695.
  18. (2008) M27-A3 Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard. (2008) National Committee for Clinical and Laboratory Standards, Wayne PA. 28(14). https://clsi.org/media/1461/m27a3_sample.pdf
  19. (2018) M07–A11 Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard. Clinical and Laboratory Standards Institute, Wayne PA. 11th edition. 38(2). https://clsi.org/media/1928/m07ed11_sample.pdf
  20. Marinescu M., Popa C.V. (2022) Pyridine compounds with antimicrobial and antiviral activities. Int. J. Mol. Sci. 23(10), 5659.
  21. Karunanidhi A., Ghaznavi-Rad E., Jeevajothi Nathan J., Joseph N., Chigurupati S., Mohd Fauzi F., Pichika M.R., Hamat R.A., Lung L.T.T., van Belkum A., Neela V. (2019) Bioactive 2-(methyldithio)oyridine-3-carbonitrile from persian shallot (Allium stipitatum Regel.) exerts broad-spectrum antimicrobial activity. Molecules. 24(6), 1003.
  22. Roseblade A., Ung A., Bebawy M. (2017) Synthesis and in vitro biological evaluation of thiosulfinate derivatives for the treatment of human multidrug-resistant breast cancer. Acta Pharm. Sinica. 38(10), 1353–1368.
  23. Stellenboom N., Hunter R., Caira M.R., Bourne S.A., Cele, K. Qwebani T., le Roex T. (2007) Synthesis and inclusion of S-aryl alkylthiosulfinates as stable allicin mimics. ARKIVOC. 9, 53–63.
  24. Mehendale H.M. (2010) 7.19 ‒ Halogenated hydrocarbons. In: Comprehensive Toxicology, 2nd edition, vol. 7. Ed. McQueen C.A. Elsevier, pp. 459–474. https://doi.org/10.1016/B978-0-08-046884-6.00824-1

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2. Fig. 1. Scheme of synthesis of thiosulfinates. Reagents and general conditions: (i) H2O2, HCOOH, 0°C; (ii) m-CPBA, CH2Cl2, -78°C → 0°C; (iii) ROH, boiling, H2SO4. The output of the product is indicated in parentheses. Designations: Me ‒ methyl group, Et ‒ ethyl group, Pr ‒ propyl group, Allyl ‒ allyl group, Py-N-oxide ‒ pyridine-N-oxide, propionic acid ‒ propionic acid.

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