Synthesis, characterization and biological activity of methotrexate-derived salts in lung cancer cells
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 <sup>1</sup>H NMR, <sup>13</sup>C NMR, and elemental analysis. The antiproliferative effects of MTX salts were studied in A459 and H1975 (lung cancer cell lines) with three promising results: [C<sub>12</sub>mim]<sub>2</sub>[MTX] (IC<sub>50</sub> = 0.55 ± 0.25) > [C<sub>10</sub>-3-picoline]<sub>2</sub>[MTX] (IC<sub>50</sub> = 0.94 ± 0.03) > [C<sub>10</sub>mim]<sub>2</sub>[MTX] (IC<sub>50</sub> = 1.71 ± 0.23) in A549. These three MTX salts also demonstrated intrinsic apoptosis, avoiding necrosis and the formation of reactive oxygen species.
Authors
- Pedro Viana Baptista (ORCID: https://orcid.org/0000-0001-5255-7095)
- Alexandra Ramos Fernandes (ORCID: https://orcid.org/0000-0003-2054-4438)
- Dário Silva (ORCID: https://orcid.org/0000-0002-2565-089X)
- Luı́s C. Branco (ORCID: https://orcid.org/0000-0003-2520-1151)
- Sandra Cordeiro (ORCID: https://orcid.org/0000-0002-3825-1695)
Institutions
- Rede de Química e Tecnologia (PT)
- Universidade Nova de Lisboa (PT)
Publication Details
- Journal
- RSC Medicinal Chemistry
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1039/d4md00960f
- Primary Topic
- Synthesis and biological activity
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Universidade Nova de Lisboa
- Applied Molecular Biosciences Unit
- Rede de Química e Tecnologia
- Laboratório Associado para a Química Verde
- Fundação para a Ciência e a Tecnologia