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Research Article

2-核碱基取代的4，6-二氨基三嗪类似物：5-氟尿嘧啶敏感和耐药结直肠癌细胞的合成和抗癌活性

卷 30, 期 26, 2023

发表于: 10 November, 2022

页: [3032 - 3049] 页: 18

弟呕挨: 10.2174/0929867329666220914112042

价格: $65

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摘要

背景：癌症仍然是全球第二大死因，结直肠癌（CRC）是第三大常见类型。尽管癌症治疗取得了重大进展，但目前对 CRC 的治疗仍然不理想。此外，5-氟尿嘧啶（5-FU）等可用化疗药物的有效性受到 CRC 获得性耐药性的限制。 方法：在这项研究中，我们提供了用于合成四种新型核碱基类似物的创新方法。同样，我们描述了这些化合物对 5-FU 敏感（HCT116）和抗性（5-FU-R-HCT116）人类 CRC 细胞增殖、迁移、聚集和粘附的影响。在这两种细胞类型中，我们合成的新型类似物以浓度和时间依赖性方式显着抑制细胞活力。这凸显了这些新型类似物的更高效力。此外，这些化合物减弱了两种细胞类型的迁移和粘附，同时促进了同型细胞间的相互作用。 结果：这些变化反映在基质金属蛋白酶（MMP-2 和 MMP-9）的下调上。此外，我们的类似物在体内表现出有效的抗血管生成活性。 结论：这些新型核碱基类似物降低了 5-FU 敏感和耐药 CRC 细胞分泌的血管内皮生长因子（VEGF）和一氧化氮（NO）的水平。总而言之，我们的数据突出了我们针对 CRC 的新型类似物的潜在化学治疗特性，包括 5-FU 抗性形式。

关键词: 结直肠癌，5-氟尿嘧啶，核碱基，类似物，2-核碱基取代的4，6-二氨基-s-三嗪类似物，恶性肿瘤。

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