Synthesis, characterization and biological activity of methotrexate-derived salts in lung cancer cells

Silva, Dário; Cordeiro, Sandra; Baptista, Pedro V.; Fernandes, Alexandra R.; Branco, Luis C.

http://hdl.handle.net/10362/185842

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Autores

Silva, Dário

Cordeiro, Sandra

Baptista, Pedro V.

Fernandes, Alexandra R.

Branco, Luis C.

Resumo(s)

Lung cancer is one of the deadliest types of cancer, and is a public health problem worldwide. Methotrexate (MTX), a class IV drug in the biopharmaceutical classification system, is a folate antagonist that has demonstrated efficacy in cancer treatment. A suitable combination of MTX as a di-anion and biocompatible counter ions allowed the modulation of their physicochemical properties. In this work, twelve MTX salts were prepared and characterized by 1H NMR, 13C NMR, and elemental analysis. The antiproliferative effects of MTX salts were studied in A459 and H1975 (lung cancer cell lines) with three promising results: [C12mim]2[MTX] (IC50 = 0.55 ± 0.25) > [C10-3-picoline]2[MTX] (IC50 = 0.94 ± 0.03) > [C10mim]2[MTX] (IC50 = 1.71 ± 0.23) in A549. These three MTX salts also demonstrated intrinsic apoptosis, avoiding necrosis and the formation of reactive oxygen species.