Synthesis and anti-HIV activity of l-2′,3′-Dideoxy-4′-selenonucleosides (l-4′-Se-ddNs)

Abstract

Based on the potent anti-HIV activity of l-2′,3′-dideoxycytidine (l-ddC), l-2′,3′-dideoxy-4′-selenonucleosides (l-4′-Se-ddNs) have been synthesized from natural chiral template, l-glutamic acid, using Pummerer-type condensation as a key step. All synthesized compounds were assayed for anti-HIV-1 activity, but none of them did show any significant antiviral activity up to 100 μM, probably due to conformational differences between l-ddC and l-4′-Se-ddC, induced by the bulky selenium atom, which might play an important role in phosphorylation by cellular kinase.

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Acknowledgements

This research was supported by grants from Mid-career Research Program (2016R1A2B3010164) and Basic Science Research Program (2018R1D1A1A02085459) of the National Research Foundation (NRF), Korea. Antiviral assay by C.-K. Lee (KRICT) is greatly appreciated.

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Correspondence to Lak Shin Jeong.

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Yu, J., Kim, G., Jarhad, D.B. et al. Synthesis and anti-HIV activity of l-2′,3′-Dideoxy-4′-selenonucleosides (l-4′-Se-ddNs). Arch. Pharm. Res. 42, 780–789 (2019). https://doi.org/10.1007/s12272-019-01157-6

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Keywords

  • Antiviral
  • l-2′,3′-Dideoxy-4′-selenonucleosides
  • l-Nucleoside
  • Pummerer-type condensation
  • l-4′-Se-ddC