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

IF 3.597 Q2 Pharmacology, Toxicology and Pharmaceutics

MedChemComm Pub Date : 2025-04-16 DOI:10.1039/D4MD00960F

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

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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 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.

Abstract Image

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甲氨蝶呤衍生盐在肺癌细胞中的合成、表征及生物活性研究。

肺癌是最致命的癌症之一，是一个全球性的公共卫生问题。甲氨蝶呤（Methotrexate， MTX）是一种叶酸拮抗剂，在生物制药分类系统中属于IV类药物，已被证明在癌症治疗中有效。MTX作为二阴离子和生物相容的反离子的适当组合允许它们的物理化学性质的调制。本文制备了12种MTX盐，并通过1H NMR、13C NMR和元素分析对其进行了表征。研究了MTX盐对A459和H1975（肺癌细胞株）的抗增殖作用，得到3个令人满意的结果：[C12mim]2[MTX] (IC50 = 0.55±0.25)，bb0 [c10 -3-吡啶]2[MTX] (IC50 = 0.94±0.03),bb1 [C10mim]2[MTX] （IC50 = 1.71±0.23）。这三种MTX盐也表现出内在的细胞凋亡，避免坏死和活性氧的形成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

MedChemComm BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL

CiteScore

4.70

自引率

0.00%

发文量

审稿时长

2.2 months

期刊介绍： Research and review articles in medicinal chemistry and related drug discovery science; the official journal of the European Federation for Medicinal Chemistry. In 2020, MedChemComm will change its name to RSC Medicinal Chemistry. Issue 12, 2019 will be the last issue as MedChemComm.