Cytotoxic Activity of Salicylic Acid-Containing Drug Models with Ionic and Covalent Binding

Ksenia S Egorova; Marina M Seitkalieva; Alexandra V Posvyatenko; Victor N Khrustalev; Valentine P Ananikov

doi:10.1021/acsmedchemlett.5b00258

Cytotoxic Activity of Salicylic Acid-Containing Drug Models with Ionic and Covalent Binding

ACS Med Chem Lett. 2015 Sep 28;6(11):1099-104. doi: 10.1021/acsmedchemlett.5b00258. eCollection 2015 Nov 12.

Authors

Ksenia S Egorova¹, Marina M Seitkalieva¹, Alexandra V Posvyatenko², Victor N Khrustalev³, Valentine P Ananikov⁴

Affiliations

¹ N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Leninsky prospect 47, Moscow 119991, Russia.
² Institute of Gene Biology, Russian Academy of Sciences , Vavilova str. 34/5, Moscow 119334, Russia ; D. Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russian Federation , Samory Mashela str., Moscow 117198, Russia.
³ Peoples' Friendship University of Russia , 6 Miklukho-Maklay Street, Moscow 117198, Russian Federation ; A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences , 28 Vavilov Street, Moscow 119991, Russian Federation.
⁴ N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences , Leninsky prospect 47, Moscow 119991, Russia ; Saint Petersburg State University , Universitetsky Prospekt 26, Stary Petergof 198504, Russia.

Abstract

Three different types of drug delivery platforms based on imidazolium ionic liquids (ILs) were synthesized in high preparative yields, namely, the models involving (i) ionic binding of drug and IL; (ii) covalent binding of drug and IL; and (iii) dual binding using both ionic and covalent approaches. Seven ionic liquids containing salicylic acid (SA-ILs) in the cation or/and in the anion were prepared, and their cytotoxicity toward the human cell lines CaCo-2 (colorectal adenocarcinoma) and 3215 LS (normal fibroblasts) was evaluated. Cytotoxicity of SA-ILs was significantly higher than that of conventional imidazolium-based ILs and was comparable to the pure salicylic acid. It is important to note that the obtained SA-ILs dissolved in water more readily than salicylic acid, suggesting benefits of possible usage of traditional nonsoluble active pharmaceutical ingredients in an ionic liquid form.

Keywords: API-IL; Drug development; active pharmaceutical ingredients; cytotoxicity; ionic liquids; salicylic acid.