Synthesis of novel 6-substituted amino-9-(beta-D-ribofuranosyl)purine analogs and their bioactivities on human epithelial cancer cells

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2018-02-01

Author

TUNÇBİLEK, MERAL
Kucukdumlu, Asligul
Guven, Ebru Bilget
Altiparmak, Duygu
Atalay, Rengül

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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-6-(4-trifluoromethylphenyl) piperazine analog (27) exhibited promising cytotoxic activity. The compound 27 was more cytotoxic (IC50 = 1-4 mu M) 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 (IC50 = 1, 3 and 1 mu M 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.

Subject Keywords

Nucleoside analogs, Microwave-assisted synthesis, Cytotoxic activity, Hepatocellular carcinoma

URI

https://hdl.handle.net/11511/62963

Journal

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

DOI

https://doi.org/10.1016/j.bmcl.2017.12.070

Collections

Graduate School of Informatics, Article

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Citation Formats

M. TUNÇBİLEK, A. Kucukdumlu, E. B. Guven, D. Altiparmak, and R. Atalay, “Synthesis of novel 6-substituted amino-9-(beta-D-ribofuranosyl)purine analogs and their bioactivities on human epithelial cancer cells,” BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, pp. 235–239, 2018, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/62963.