Marina SEITKALIEVA1, Anna V. VAVINA 1, Ksenia S. EGOROVA1, Evgeniy G. GORDEEV1, Valentine P. ANANIKOV1
1N.D. Zelinsky Institute of Organic Chemistry, Moscow, Russian Federation
One of the important ionic liquids (ILs) application is their use for biological aids. ILs are used for the dissolution, extraction, storage, and transportation of biologically active molecules. Many ILs themselves exhibit biological activities, including cytotoxic and antimicrobial ones. [1-2] The potential pharmaceutical application, comprising the transformation of active pharmaceutical ingredients (API) into ILs form (API-ILs), was proposed and studied widely. This strategy aims at enhancing the API solubility, bioavailability and stability. To do this, poorly soluble in water biologically active compounds converted into the form of ILs using one of three approaches: (a) API as cation or anion, (b) API covalently linked to an IL cation or anion, (c) ionic and covalent approaches for one or two API into one IL. [3]
In our work, we synthesized ILs based on the known structural frameworks of imidazolium, pyridinium, and cholinium ILs with naturally occurring cinnamic acid. [4] Cinnamic acid has a known biological activity, but is poorly soluble in water. Using various combinations of IL and cinnamic acid allowed to modulate physicochemical properties and biological activity of the synthesized compounds. The structure-activity interactions were analyzed using molecular dynamics.
Acknowledgements
The work was supported by the Russian Science Foundation (RSF Project #21-73-10262).
References
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[2] Vereshchagin A.N., Frolov N.A., Egorova K.S., Seitkalieva M.M., Ananikov V.P. "Quaternary Ammonium Compounds (QACs) and Ionic Liquids (ILs) as Biocides: From Simple Antiseptics to Tunable Antimicrobials", Int. J. Mol. Sci., 2021, 22(13), 6793.
[3] Egorova K. S., Seitkalieva M. M., Posvyatenko A. V., Khrustalev V. N., Ananikov V. P., "Cytotoxic Activity of Salicylic Acid-Containing Drug Models with Ionic and Covalent Binding", ACS Med. Chem. Lett., 2015, 6, 1099–1104.
[4] Vavina A.V., Seitkalieva M.M., Posvyatenko A.V., Gordeev E.G., Strukova E.N., Egorova K.S., Ananikov V.P. "Merging structural frameworks of imidazolium, pyridinium, and cholinium ionic liquids with cinnamic acid to tune solution state behavior and properties", J. Mol. Liq., 2022, 118673.