甲氨蝶呤衍生盐类在肺癌细胞中的合成、表征及生物活性

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

作者信息

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

机构信息

LAQV-REQUIMTE, Nova School of Science and Technology, NOVA University Lisbon 2829-516 Caparica Portugal

Associate Laboratory i4HB - Institute for Health and Bioeconomy, NOVA School of Science and Technology, NOVA University Lisbon 2829-516 Caparica Portugal

出版信息

RSC Med Chem. 2025 Apr 16. doi: 10.1039/d4md00960f.

DOI:10.1039/d4md00960f

PMID:40453178

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12121626/

Abstract

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 H NMR, 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: [Cmim][MTX] (IC = 0.55 ± 0.25) > [C-3-picoline][MTX] (IC = 0.94 ± 0.03) > [Cmim][MTX] (IC = 1.71 ± 0.23) in A549. These three MTX salts also demonstrated intrinsic apoptosis, avoiding necrosis and the formation of reactive oxygen species.

摘要

肺癌是最致命的癌症类型之一，也是一个全球性的公共卫生问题。甲氨蝶呤（MTX）是生物药剂学分类系统中的IV类药物，是一种叶酸拮抗剂，已在癌症治疗中显示出疗效。MTX作为二价阴离子与生物相容性抗衡离子的合适组合能够调节其物理化学性质。在这项工作中，制备了十二种MTX盐，并通过1H NMR、13C NMR和元素分析对其进行了表征。在A459和H1975（肺癌细胞系）中研究了MTX盐的抗增殖作用，得到了三个有前景的结果：在A549中，[Cmim][MTX]（IC50 = 0.55 ± 0.25）>[C-3-吡啶][MTX]（IC50 = 0.94 ± 0.03）>[C2mim][MTX]（IC50 = 1.71 ± 0.23）。这三种MTX盐还表现出内在凋亡，避免了坏死和活性氧的形成。