Biological activity of levoglucosenone and its derivatives (analytical review)

Introduction. Levoglucosenone (LG) is an enone of a carbohydrate nature obtained by acid pyrolysis of cellulose. Given the high synthetic potential and availability of LG, we found it interesting to study its potential as a platform for the synthesis of a wide range of biologically active compounds to identify the biological activity of the derivatives obtained.

Materials and methods. The prediction of the biological properties of LG and its derivatives synthesized in the Laboratory of cyclic pharmacophore systems of the Ufa Institute of Chemistry was carried out using the PASS-computer software. Biological tests of LG and its derivatives were performed.

Results. The acute toxicity of LG was studied for the first time, and cytotoxic, fungistatic, bacteriostatic, anti-aggregation, anticoagulant and antioxidant properties of LG and its derivatives were demonstrated.

Limitations. Limited financial availability of biological trials of synthesized LG demonstrated.

Conclusion. Of course, the LG molecule deserves the attention of researchers with its structure activated for further transformations and the study of the biological activity in LG and its derivatives. Leaders in biological activity have been identified among the compounds studied, with LG and its derivatives being chiral organic molecules and of interest for libraries of compounds with necessary biological activities. This article will be useful for scientists interested in searching for new promising chiral molecules derived from available natural objects to identify their pharmacological potential with the aim of further use in medicine.

Compliance with ethical standards. Protocol № 8 of the Seminar on Organic and Bioorganic Chemistry of the Ufa Institute of Chemistry dated 04/10/2025.

Contribution:
Akhmetdinova N.P. – collection of material and data processing, writing text;
Faizullina L.Kh. – concept and design of the study, editing;
Samorodov A.V. – concept and design of the study, editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Funding. The research was supported by the State Assignment of the Ufa Institute of Chemistry, on the topic «Development of strategies and methods for the targeted synthesis of practically important substances based on fundamental studies of the properties of natural compounds and organic synthesis products» (state registration № 125020601627-6).

Received: April 23, 2025 / Accepted: December 2, 2025 / Published: March 13, 2026

1. Miftakhov M.S., Valeev F.A., Gaisina I.N. Levoglucosenone: the properties, reactions, and use in fine organic synthesis. Uspekhi khimii. 1994; 63(10): 922–36. https://doi.org/10.1070/RC1994v063n10ABEH000123 (in Russian)

2. Witczak Z.J. Levoglucosenone and Levoglucosans: Chemistry and Applications. ATL Press; 1994.

3. Witczak Z.J. Carbohydrate therapeutic: new developments and strategies. Carbohydr. Drug Des. 2006; 932: 25–46. https://doi.org/10.1021/bk-2006-0932.ch002

4. Sarotti A.M., Zanardi M.M., Spanevello R.A., Suarez A.G. Recent applications of levoglucosenone as chiral synthon. Curr. Org. Synth. 2012; 9(4): 439–59. https://doi.org/10.2174/157017912802651401

5. Comba M.B., Tsai Y.H., Sarotti A.M., Mangione M.I., Suárez A.G., Spanevello R.A. Levoglucosenone and its new applications: valorization of cellulose residues. Eur. J. Org. Chem. 2018; 2018(5): 590–604. https://doi.org/10.1002/ejoc.201701227 https://elibrary.ru/yghrql

6. Available at: https://www.way2drug.com/PassOnline/predict.php

7. Mironov A.N., ed. Methodological Recommendations for Preclinical Study of Antitumour Activity of Drugs. Guidelines for preclinical studies of drugs. Part 1 [Metodicheskie rekomendatsii po doklinicheskomu izucheniyu protivoopukholevoi aktivnosti lekarstvennykh sredstv. Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv. Chast’ 1]. Moscow: Grif and K; 2012: 642–56. https://elibrary.ru/sdewmp (in Russian)

8. Mironov A.N., Bunatyan N.D. Manual on Conducting Preclinical Studies of Drugs. Part 1 [Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv. Chast’ 1]. Moscow: Grif and K; 2012. (in Russian)

9. Gurevich K.G., Urakov A.L., Klen E.E., Samorodov A.V., Nikitina I.L., Khaliullin F.A., et al. Synthesis and biological activity of ethyl 2-[8-arylmethylidenehydrazino-3-methyl-7-(1-oxothietan-3-yl)xanth-1-yl]acetates. Pharmaceutical Chemistry Journal. 2020; 54(3): 213–9. https://doi.org/10.1007/s11094-020-02182-2 https://elibrary.ru/qpedun

10. Born G.V., Garrod D. Photometric demonstration of aggregation of slime mould cells showing effects of temperature and ionic strength. Nature. 1968; 220(5167): 616–8. https://doi.org/10.1038/220616a0

11. Faizullina L.Kh., Khalilova Yu.A., Valeev F.A., Pavlov V.N., Samorodov A.V. Preparation of the adduct of levoglucosenone and resorcinol and its in vitro antiplatelet and anticoagulant activity. Chem. Heterocycl. Comp. 2021; 57(9): 966–9. https://doi.org/10.1007/s10593-021-03007-0 https://elibrary.ru/mvrfke

12. Khaliullin F.A., Mamatov Z.K., Timirkhanova G.A., Samorodov A.V., Bashirova L.I. Synthesis, antiaggregant, and antioxidant activity of 2-{[1-iso-butyl-3-methyl-7-(thietanyl-3)xanthin-8-yl]thio}acetic acid salts. Pharmaceutical Chemistry Journal. 2020; 54(9): 891–6. https://doi.org/10.1007/s11094-020-02293-w https://elibrary.ru/hkvozb

13. Faizullina L.Kh., Karamisheva L.Sh., Yakupova L.R., Migranov A.R., Safiullin R.L., Valeev F.A., et al. Synthesis and evolution of antioxidant, anticoagulation and antiagregation activities of levoglucosenone adducts containing methyl substituted of phenyl fragments. Khimiko-farmatsevticheskii zhurnal. 2024; 58(6): 48–53. https://doi.org/10.30906/0023-1134-2024-58-6-48-53 https://elibrary.ru/trdsvg (in Russian)

14. Yakupova L.R., Khayrullina V., Gerchikov A.Ya., Safiullin R.L., Baimuratova G.R. Kinetics of the liquid-phase oxidation of 1,4-dioxane in the presence of inhibitors. Kinetics and Catalysis. 2008; 49(3): 366–70. https://doi.org/10.1134/S0023158408030075 https://elibrary.ru/llmvbn

15. Sharipov B.T., Davidova A.N., Valeev F.A., Ryabova A.S., Galimzyanova N.F. Synthesis and fungicidal activity of methylsulfanyl methyl esters of levoglucosenone derivatives. Chem. Heterocycl. Compd. 2019; 55(1): 31–7. https://doi.org/10.1007/s10593-019-02415-7 https://elibrary.ru/rzmfri

16. Grever M.R., Schepartz S.A., Chabner B.A. The National Cancer Institute: cancer drug discovery and development program. Semin. Oncol. 1992; 19(6): 622–38.

17. Boyd M.R., Paull K.D. Some practical considerations and applications of the National Cancer Institute in vitro anticancer drug discovery screen. Drug Dev. Res. 1995; 34(2): 91–109. https://doi.org/10.1002/ddr.430340203

18. Shoemaker R.H. The NCI60 human tumour cell line anticancer drug screen. Nat. Rev. Cancer. 2006; 6(10): 813–23. https://doi.org/10.1038/nrc1951

19. Faizullina L.Kh. Levoglucosenone – a bio-renewable platform in stereocontrolled syntheses and transformations of amino derivatives and ∆3-adducts: Diss. Ufa; 2022. (in Russian)

20. Valgimigli L. Lipid peroxidation and antioxidant protection. Biomolecules. 2023; 13(9): 1291. https://doi.org/10.3390/biom13091291