Synthesis of ribavirin 1,2,3- and 1,2,4-triazolyl analogs with changes at the amide and cytotoxicity in breast cancer cell lines

Abstract

We report the synthesis and cytotoxicity in MCF-7 and MDA-MB-231 breast cancer cells of novel 1,2,3- and 1,2,4-triazolyl analogs of ribavirin. We modified ribavirin’s carboxamide moiety to test the effects of lipophilic groups. 1-β-D-Ribofuranosyl-1H-1,2,3-triazoles were prepared using Click Chemistry, whereas an unprecedented application of a prior 1,2,4-triazole ring synthesis was used for 1-β-D-ribofuranosyl-1H-1,2,4-triazole analogs. Though cytotoxicity was mediocre and there was no correlation with lipophilicity, we discovered that a structurally similar concentrative nucleoside transporter 2 (CNT2) inhibitor was modestly cytotoxic (MCF-7 IC₅₀ of 42 µM). These syntheses could be used to efficiently investigate variation in the nucleobase.

Keywords:

• Nucleoside analogs
• initiation factor
• triazole
• click chemistry

Acknowledgements

H.W. thanks the UNK Summer Student Research Program (SSRP) for financial support. This work was also supported by the UNK Research Services Council (RSC) and the Nebraska EPSCoR Undergraduate Research Experiences (URE) at Small Colleges and Universities Program. Funding for S.C. and the tissue culture lab used for cell survival experiments was provided by the Nebraska IDeA Networks of Biomedical Research Excellence (INBRE) program.

Disclosure statement

The authors declare no competing financial interest.

Additional information

Funding

H.W. thanks the UNK Summer Student Research Program (SSRP) for financial support. This work was also supported by the UNK Research Services Council (RSC) and the Nebraska EPSCoR Undergraduate Research Experiences (URE) at Small Colleges and Universities Program. Funding for S.C. and the tissue culture lab used for cell survival experiments was provided by the Nebraska IDeA Networks of Biomedical Research Excellence (INBRE) program.