New ionic liquids based on 5-fluorouracil: Tuning of BSA binding and cytotoxicity

Khachatrian, Artashes A.; Mukhametzyanov, Timur A.; Salikhov, Ramazan Z.; Klimova, Alexandra E.; Gafurov, Zufar N.; Kantyukov, Artyom O.; Yakhvarov, Dmitry G.; Garifullin, Bulat F.; Mironova, Diana A.; Voloshina, Alexandra D.; Solomonov, Boris N.

doi:10.1016/j.ijbiomac.2023.128642

Cited by 1 publication

(1 citation statement)

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“…The conversion of active pharmaceutical ingredients (APIs) into ionic liquid (IL) formulations is a relatively novel and effective approach for drug delivery, tailoring APIs’ solubility and bioavailability, improving their thermal and storage stability, increasing dissolution, resolving problems with their polymorphic conversion, regulating drug release, boosting APIs’ permeability, and/or modulating their cytotoxicity on tumor cells [ 33 , 34 , 35 , 36 ].…”

Section: Introductionmentioning

confidence: 99%

Tuning of the Anti-Breast Cancer Activity of Betulinic Acid via Its Conversion to Ionic Liquids

Ossowicz-Rupniewska,

Klebeko,

Georgieva

et al. 2024

Pharmaceutics

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Betulinic acid (BA) is a natural pentacyclic triterpene with diverse biological activities. However, its low water solubility limits its pharmaceutical application. The conversion of pharmaceutically active molecules into ionic liquids (ILs) is a promising strategy to improve their physicochemical properties, stability, and/or potency. Here, we report the synthesis and characterization of 15 novel ILs containing a cation ethyl ester of a polar, non-polar, or charged amino acid [AAOEt] and an anion BA. Except for [ValOEt][BA], we observed preserved or up to 2-fold enhanced cytotoxicity toward hormone-dependent breast cancer cells MCF-7. The estimated IC50 (72 h) values within the series varied between 4.8 and 25.7 µM. We found that the most cytotoxic IL, [LysOEt][BA]2, reduced clonogenic efficiency to 20% compared to that of BA. In addition, we evaluated the effect of a 72 h treatment with BA or [LysOEt][BA]2, the most cytotoxic compound, on the thermodynamic behavior of MCF-7 cells. Based on our data, we suggest that the charged amino acid lysine included in the novel ILs provokes cytotoxicity by a mechanism involving alteration in membrane lipid organization, which could be accompanied by modulation of the visco–elastic properties of the cytoplasm.

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