Obtaining and Determining Antiviral and Antibacterial Activity of S-Esters of 4-R-Aminobenzenethiosulfonic Acid

: pp. 315 - 324
Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Laboratory of Immunobiology
Department of Immunology of Infectious Diseases, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Laboratory of Immunobiology
Institute of Physical-Organic Chemistry and Coal Chemistry named after L. M. Lytvynenko of the National Academy of Sciences of Ukraine, Department of Technology of Biologically Active Substances, Pharmacy & Biotechnology, Lviv National Polytechnic University
Department of Technology of Biologically Active Substances, Pharmacy & Biotechnology, Lviv National Polytechnic University
Department of Technology of Biologically Active Substances, Pharmacy & Biotechnology, Lviv National Polytechnic University
Department of Technology of Biologically Active Substances, Pharmacy & Biotechnology, Lviv National Polytechnic
Department of Technology of Biologically Active Substances, Pharmacy & Biotechnology, Lviv National Polytechnic University
Lviv Polytechnic National University
Alpinus Chemia Sp. z o. o.
Lviv Polytechnic National University
Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Laboratory of Immunobiology

A number of S-esters of 4-R-aminobenzene¬thiosulfonic acids were synthesized via alkylation of the sodium salt of 4-acetylaminobenzenethiosulfonic acid with various alkylating agents and acylation of the corresponding esters of 4-aminobenzenethiosulfonic acid with metha-cryloyl chloride. For obtaining S-methyl 4-(acetyla-mino)benzenesulfonothioate, it was developed a synthetic technique corresponding to the basic principles of "green chemistry". The degree of compound cytotox-icity was measured by determining A-549 cell growth using colorimetric method. The antibacterial activity of the thiosulfonates was determined by the agar diffusion test and the antiviral action by their cytopathic effect at TCID50 value.

  1. Kubin, C.J.; McConville, T.H.; Dietz, D.; Zucker, J.; May, M.; Nelson, B.; Istorico, E.; Bartram, L.; Small-Saundres, J.; Sobieszczyk, M.E.; et al. Characterization of Bacterial and Fungal Infections in Hospitalized Patients with Coronavirus Disease 2019 and Factors Associated with Health Care-Associated Infections. Open Forum Infect. Dis. 2021, 8, ofab201. https://doi.org/10.1093/ofid/ofab201
  2. Reddy, R.J.; Waheed, Md.; Kumar J.J. A Straightforward and Convenient Synthesis of Functionalized Allyl Thiosulfonates and Allyl Disulfanes. RSC Adv. 2018, 8, 40446-40453. https://doi.org/10.1039/c8ra06938g
  3. Mampuys, P.; McElroy, C.R.; Clark, J.; Orru, R.V.A.; Maes, B.U.W. Thiosulfonates as Emerging Reactants: Synthesis and Applications. Adv. Synth. Catal. 2020, 362, 3-64. https://doi.org/10.1002/adsc.201900864
  4. Batiha, G.E.S.; Beshbishy, A.M.; Wasef, L.G.; Elewa Y.H.A., Al-Sagan, A.A.; Abd El-Hack, M.E.; Taha, A.E.; Abd-Elhakim, Y.M.; Devkota, H.P. Chemical Constituents and Pharmacological Activities of Garlic (Allium sativum L.). Nutrients 2020, 12, 872. https://doi.org/10.3390/nu12030872
  5. Gabriele, E.; Ricci, C.; Meneghetti, F.; Ferri, N.; Asai, A.; Sparatore, A. Methanethiosulfonate Derivatives as Ligands of the STAT3-SH2 Domain. J Enzyme Inhib Med Chem. 2017, 32, 337-344. http://dx.doi.org/10.1080/14756366.2016.1252757
  6. Alseeni, M.N., Allheani, E. M., Qusti, S.Y., Qusti, N. Y., Alotaibi, S.A., Alotaibi, H.A.. Antimicrobial Activities of Some Plant Extracts against Some. Int. j. pharm. biol. sci. 2019, 14, 01-10.
  7. Sharma, N.; Behl, T.; Singh, S.; Bansal, A.; Kumari Singh, S.; Zahoor, I. Expatiating the Therapeutic Profile of Garlic (Allium sativum): a Bench to Bedside Approach. Biointerface Res. Appl. Chem. 2021, 11, 14225-14239. https://doi.org/10.33263/BRIAC116.1422514239
  8. Sorlozano-Puerto, A.; Albertuz-Crespo, M.; Lopez-Machado, I.; Gil-Martinez, L.; Ariza-Romero, J. J.; Maroto-Tello, A.; Baños-Arjona, A.; Gutierrez-Fernandez, J. Antibacterial and Antifungal Activity of Propyl-Propane-Thiosulfinate and Propyl-Propane-Thiosulfonate, Two Organosulfur Compounds from Allium cepa: In Vitro Antimicrobial Effect via the Gas Phase. Pharmaceuticals 2021, 14, 21. https://doi.org/10.3390/ph14010021
  9. Gruhlke, M.C.H.; Nicco, C.; Batteux, F.; Slusarenko, A.J. The Effects of Allicin, a Reactive Sulfur Species from Garlic, on a Selection of Mammalian Cell Lines. Antioxidants (Basel) 2016, 6, 1. https://doi.org/10.3390/antiox6010001
  10. Llana-Ruiz-Cabello, M.; Gutiérrez-Praena, D.; Puerto, M.; Pichardo, S.; Javier Moreno, F.; Baños, A.; Nuñez, C.; Guillamón, E.; Cameán, A. M. Acute Toxicological Studies of the Main Organosulfur Compound Derived from Allium sp. Intended to be Used in Active Food Packaging. Food Chem. Toxicol. 2015, 82, 1-11. https://doi.org/10.1016/j.fct.2015.04.027
  11. Zilbeyaz, K.; Oztekin, A.; Kutluana, E.G. Design and Synthesis of Garlic-Related Unsymmetrical Thiosulfonates as Potential Alzheimer's Disease Therapeutics: In Vitro and In Silico Study. Bioorg. Med. Chem. 2021, 40, 116194. https://doi.org/10.1016/j.bmc.2021.116194
  12. Oriabinska, L.B.; Starovoitova, S.O.; Vasylyuk, S.V.; Novikov, V.P.; Lubenets, V.I. Ethylthiosulfanilate Effect on Candida Tropicalis. Ukr. Biochem. J. 2017, 89, 70-76. https://doi.org/10.15407/ubj89.05.070
  13. Martyrosian, I.A.; Pakholiuk, O.V.; Semak, B.D.; Komarovska-Porokhnyavets, O.; Lubenets, V.I.; Pambuk, S.A. New Technologies of Effective Protection of Textiles Against Microbiological Damage. Nanosistemi, Nanomateriali, Nanotehnologii 2019, 17, 621-636. https://doi.org/10.15407/nnn
  14. Lubenets, V.; Stadnytska, N.; Baranovych, D.; Vasylyuk, S.; Karpenko, O.; Havryliak, V.; Novikov, V. Thiosulfonates. The Prospective Substances against Fungal Infections. In Fungal Infection; Silva de Loreto, É.; Moraes Tondolo, J.S., Eds.; 2019. http://dx.doi.org/10.5772/intechopen.84436
  15. Liubas, N.; Iskra, R.; Stadnytska, N.; Monka, N.; Havryliak, V.; Lubenets, V. Antioxidant Activity of Thiosulfonate Compounds in Experiments In Vitro and In Vivo. Biointerface Res. Appl. Chem 2022, 12, 3106-3116. https://doi.org/10.33263/BRIAC123.31063116
  16. Kotyk, B.I.; Iskra, R.Ya.; Slivinska, O.M.; Liubas, N.M.; Pylypetes, A.Z.; Lubenets, V.I.; Pryimych, V.I. Effects of Ethylthiosulfanylate and Chromium (VI) on the State of Pro/Antioxidant System in Rat Liver. Ukr. Biochem. J. 2020, 92, 78-86. https://doi.org/10.15407/ubj92.05.078
  17. Halenova, T.I.; Nikolaeva, I.V.; Nakonechna, A.V.; Bolibrukh, K.B.; Monka, N.Y.; Lubenets, V.I.; Savchuk, O.M.; Novikov, V.P.; Ostapchenko, L.I. The Search of Compounds with Antiaggregation Activity Among S-esters of Thiosulfonic Acids. Ukr. Biochem. J. 2015, 87, 83-92. https://doi.org/10.15407/ubj87.05.083
  18. Dmitryjuk, M.; Szczotko, M.; Kubiak, K.; Trojanowicz, R.; Parashchyn, Z.; Khomitska, H.; Lubenets, V. S-Methyl-(2-Methoxycarbonylamino-Benzimidazole-5) Thiosulfonate as a Potential Antiparasitic Agent-Its Action on the Development of Ascaris suum Eggs In Vitro. Pharmaceuticals (Basel) 2020, 13, 332. https://doi.org/10.3390/ph13110332
  19. Lubenets, V.I.; Vasylyuk, S.V.; Novikov, V.P. Synthesis of S-(3-chloroquinoxalin-2-YL) Esters of Aliphatic and Aromatic Thiosulfonic Acids. Chem. Heterocycl. Compd. 2005, 41, 1547-1548. https://doi.org/10.1007/s10593-006-0039-9
  20. Vasylyuk, S.; Komarovska-Porokhnyavets, O.; Novikov, V.; Lubenets, V. Modification of Alkyl Esters of 4-Aminobenzenethiosulfonic Acid by S-triazine Fragment and Investigation of their Growth-Regulative Activity. Chem. Chem. Technol. 2018, 12, 24-28. https://doi.org/10.23939/chcht12.01.024
  21. Kuz'menko, L.; Avdeenko, A.; Konovalova, S.; Vasylyuk, S.; Fedorova, O.; Monka, N.; Krychkovska, A.; Lubenets, V. Synthesis and Study of Pesticidal Activity of Some N-Arylthio-1,4-Benzoquinone Imines. Biointerface Res. Appl. Chem. 2019, 9, 4232-4238. https://doi.org/10.33263/BRIAC95.232238
  22. Cheng, Y.; Pham, A.-T.; Kato, T.; Lim, B.; Moreau, D.; Lopez-Andarias, J.; Zong, L.; Sakai, N.; Matile, S. Inhibitors of Thiol-Mediated Uptake. Chem. Sci. 2021, 12, 626-631. https://doi.org/10.1039/D0SC05447J
  23. Focke, M.; Feld, A.; Lichtenthaler, K. Allicin, a Naturally Occurring Antibiotic from Garlic, Specifically Inhibits Acetyl-CoA Synthesis. FEBS Lett. 1990, 261, 106-108. https://doi.org/10.1016/0014-5793(90)80647-2
  24. Roth, P.J.; Theato, P. Thiol-Thiosulfonate Chemistry in Polymer Science: Simple Fictionalization of Polymers via Disulfide linkages. In Thiol-X Chemistries in Polymer and Materials Science; Lowe, A., Bowman, C., Eds.; Abingdon: Nashville, TN, USA, 2013; pp 76-94.
  25. Borlinghaus, J.; Albrecht, F.; Gruhlke, M.C.H.; Nwachukwu, I.D; Slusarenko, A.J. Allicin: Chemistry and Biological Properties. Molecules 2014, 19, 12591-12618. https://doi.org/10.3390/molecules190812591
  26. Whitley, R.J.; Roizman, B. Herpes Simplex Virus Infections. Lancet 2001, 357, 1513-1518. https://doi.org/10.1016/S0140-6736(00)04638-9
  27. Looker, K.J.; Welton, N.J.; Sabin, K. M.; Dalal, S.; Vickerman, P.; Prof, Turner, K.M.E.; Boily, M.-C.; Gottlieb, S. L. Global and Regional Estimates of the Contribution of Herpes Simplex Virus Type 2 Infection to HIV Incidence: A Population Attributable Fraction Analysis Using Published Epidemiological Data. Lancet Infect. Dis. 2019, 20, 240-249. https://doi.org/10.1016/S1473-3099(19)30470-0
  28. Reid, G.E.; Lynch, J.P.; Weigt, S.; Sayah, D.; Belperio, J.A.; Grim, S. A.; Clark, N.M. Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes. Semin Respir Crit Care Med. 2016, 37, 603-630. https://doi.org/10.1055%2Fs-0036-1584793
  29. Lubenets, V.; Karpenko, O.; Ponomarenko, M.; Zahoriy, G.; Krychkovska, A, Novikov V. Development of New Antimicrobial Compositions of Thiosulfonate Structure. Chem. Chem. Technol. 2013, 7, 119-124. https://doi.org/10.23939/chcht07.02.119
  30. Lubenets, V.; Vasylyuk, S.; Monka, N.; Bolibrukh, K.; Koma-rovska-Porokhnyavets, O.; Baranovych, D.; Musyanovych, R.; Zaczynska, E,; Czarny, A.; Nawrot, U. et al. Synthesis and Antimi-crobial Properties of 4-Acylaminobenzenethiosulfoacid S-Esters. Saudi. Pharm. J. 2017, 25, 266-274. https://doi.org/10.1016/j.jsps.2016.06.007
  31. Smith, C.D.; Craft, D.W.; Shiromoto, R.S.; Yan, P.O. Alternative Cell Line for Virus Isolation. J. Clin. Microbiol. 1986, 24, 265-268. https://doi.org/10.1128/jcm.24.2.265-268.1986
  32. Hansen, M.B.; Nielsen, S.E.; Berg, K. Re-examination and Further Development of a Precise and Rapid dye Method for Measuring Cell Growth/cell Kill. J. Immunol. Methods 1989, 119, 203-210. https://doi.org/10.1016/0022-1759(89)90397-9
  33. Heydari, S.; Habibi, D.; Faraji, A. A Green and Efficient Solvent- and Catalyst-Free Ultrasonic Dibenzylation Procedure. Chem. Chem. Technol. 2022, 16, 126-132. https://doi.org/10.23939/chcht16.01.126
  34. Kusuma, H.; Putri, D.; Dewi, I.; Mahfud, M. Solvent-free Microwave Extraction as the Useful Tool for Extraction of Edible Essential Oils. Chem. Chem. Technol. 2016, 10, 213-218. https://doi.org/10.23939/chcht10.02.213
  35. Starchevskyy, V.; Bernatska, N.; Typilo, I.; Oliynyk, L.; Strogan, O. Establishment of the Regularities of the Concentrations Change of Microorganisms and Water-Soluble Compounds in Polluted Water After Ultrasound Treatment. Chem. Chem. Technol. 2021, 15, 408-413. https://doi.org/10.23939/chcht15.03.408
  36. Lubenets, V.; Yarish, M.E.; Vid, L.V. ChemInfrom Abstract: Synthesis of Acylation Sulfanilic Esters. Zh. Org. Khim. 1987, 23, 157-161. https://doi:10.1002/chin.198723133
  37. Manual of Clinical Microbiology, 6th edition; Murray, P.R.; Baron, E.J.; Pfaller, M.A., Eds.; ASM Press: Washington, 1995.
  38. Pfaller, M.A. National Committee for Clinical Laboratory Standard, Reference method for broth dilution antifungal susceptibility tes¬ting of yeasts; approved standard - second edition M-38. Conidium For¬ming Filamentous Fungi: Proposed Standard. NCCLS. 1998, 22, M27-A2.
  39. Cutler, R.R.; Odent, M.; Hajj, H.; Maharjan, S.; Bennett, N.; Josling, P.; Ball, V.; Hatton, P.; Dall'antonia, M. In vitro Activity of an Aqueous Allicin Extract and a Novel Allicin Topical Gel Formulation against Lancefield Group B Streptococci. J. Antimicrob. Chemother. 2009, 63, 151-154. https://doi.org/10.1093/jac/dkn457
  40. Weber, N.D.; Andersen, D.O.; North, J.A.; Murray, B.K.; Lawson, L.D.; Hughes, B.G. In vitro Virucidal Effects of Allium Sativum (Garlic) Extract and Compounds. Planta Med. 1992, 58, 417-423. https://doi.org/10.1055/s-2006-961504