论文部分内容阅读
目的为了提高DNA甲基转移酶抑制剂氮杂胞苷的稳定性,降低其细胞毒作用,以氮杂胞苷为先导化合物,设计并合成了6-氨基-4-烷基/芳基-1-吡喃糖基-1,3,5-三嗪-2(1H)-酮和4-氨基-6-烷基-1,3,5-三嗪-2-基-1-硫代-吡喃糖苷两类化合物。方法以眯基脲(或眯基硫脲)与原酸酯(或苯甲酸甲酯)为起始原料,经5步反应合成目标化合物;以氮杂胞苷为阳性对照药,采用MTT法评价了目标化合物对人白血病细胞HL-60和人乳腺癌细胞MCF-7的体外抗增殖活性及与全反式维甲酸(all-trans retinoic acid,ATRA)的联合用药情况。结果与讨论合成了16个未见文献报道的化合物,其结构经1H-NMR谱和MS谱确证;与氮杂胞苷相比,目标化合物细胞毒作用均显著降低,具有中等强度的细胞生长抑制作用;吡喃糖/双糖硫苷4-胺基-6-甲基-1,3,5-三嗪-2-基-1-硫代-6’-去氧-α-L-吡喃甘露糖苷(化合物7g)和ATRA联合用药能增强抗M CF-7增殖活性,有进一步研究的价值。
Aim To improve the stability and reduce the cytotoxicity of azacytidine, a DNA methyltransferase inhibitor, azacitidine was used as the lead compound to design and synthesize 6-amino-4-alkyl / aryl-1 -pyranosyl-1,3,5-triazine-2 (1H) -one and 4-amino-6-alkyl-1,3,5-triazin-2-yl-1-thio-pyridine Two kinds of glycosides compounds. Methods The target compound was synthesized via 5 steps using squarylium (or squalethiourea) and orthoester (or methyl benzoate) as starting materials. Azacitidine was used as a positive control and MTT assay The target compounds against human leukemia cells HL-60 and human breast cancer cells MCF-7 in vitro anti-proliferative activity and all-trans retinoic acid (all-trans retinoic acid, ATRA) combination of the situation. RESULTS AND DISCUSSION Sixteen compounds that were not reported in the literature were synthesized and their structures were confirmed by 1H-NMR and MS spectra. Compared with azacytidine, the cytotoxic effects of the target compounds were significantly reduced, with moderate intensity of cell growth inhibition Pyranose / disacosyl 4-amino-6-methyl-1,3,5-triazin-2-yl-1-thioxo-6’-deoxy-α-L-pyran The combination of mannoside (compound 7g) and ATRA can enhance the anti-proliferative activity of M-CF-7, which has the value of further research.