Tuncbilek Meral, Kucukdumlu Aslıgul, Guven Ebru Bilget, Altiparmak Duygu, Cetin-Atalay Rengul
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ankara University, 06100 Ankara, Turkey.
Bioorg Med Chem Lett. 2018 Feb 1;28(3):235-239. doi: 10.1016/j.bmcl.2017.12.070. Epub 2018 Jan 2.
New nucleoside derivatives with nitrogen substitution at the C-6 position were prepared and screened initially for their in vitro anticancer bioactivity against human epithelial cancer cells (liver Huh7, colon HCT116, breast MCF7) by the NCI-sulforhodamine B assay. N-(4-trifluoromethylphenyl)piperazine analog (27) exhibited promising cytotoxic activity. The compound 27 was more cytotoxic (IC = 1-4 μM) than 5-FU, fludarabine on Huh7, HCT116 and MCF7 cell lines. The most potent nucleosides (11, 13, 16, 18, 19, 21, 27, 28) were further screened for their cytotoxicity in hepatocellular cancer cell lines. The compound 27 demonstrated the highest cytotoxic activity against Huh7, Mahlavu and FOCUS cells (IC = 1, 3 and 1 μM respectively). Physicochemical properties, drug-likeness, and drug score profiles of the molecules showed that they are estimated to be orally bioavailable. The results pointed that the novel derivatives would be potential drug candidates.
制备了在C-6位具有氮取代的新型核苷衍生物，并通过美国国立癌症研究所的磺酰罗丹明B试验，初步筛选了它们对人上皮癌细胞（肝癌Huh7、结肠癌HCT116、乳腺癌MCF7）的体外抗癌生物活性。N-(4-三氟甲基苯基)哌嗪类似物(27)表现出有前景的细胞毒性活性。化合物27在Huh7、HCT116和MCF7细胞系上比5-氟尿嘧啶、氟达拉滨具有更强的细胞毒性(IC=1-4μM)。对最具活性的核苷(11、13、16、18、19、21、27、28)进一步筛选其在肝癌细胞系中的细胞毒性。化合物27对Huh7、Mahlavu和FOCUS细胞表现出最高的细胞毒性活性(IC分别为1、3和1μM)。这些分子的物理化学性质、类药性和药物评分概况表明，它们预计具有口服生物利用度。结果表明，这些新型衍生物可能是潜在的药物候选物。
