Design, synthesis, and anticancer activity of C8-substituted-4′-thionucleosides as potential HSP90 inhibitors

Shuhao Qu, Varughese A. Mulamoottil, Akshata Nayak, Seungyeon Ryu, Xiyan Hou, Jayoung Song, Jinha Yu, Pramod K. Sahu, Long Xuan Zhao, Sun Choi, Sang Kook Lee, Lak Shin Jeong

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

A series of C8-substituted-4′-thioadenosine analogs 3a–3g, 15, and 17 and their truncated derivatives 4a–4j, 23–25, and 27 have been successfully synthesized from D-ribose and D-mannose, respectively, employing Pummerer type or Vorbrüggen condensation reactions and the functionalization at the C8-position of nucleobase via Stille coupling or nucleophilic aromatic substitution reactions as key steps. All the synthesized compounds were assayed for their HSP90 inhibitory activity, but they were found to be inactive up to 100 μM. However, the 8-iodo derivatives 15, 17, and 27 exhibited potent anticancer activity, indicating that different mechanism of action might be involved in their biological activity.

Original languageEnglish
Pages (from-to)3418-3428
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume24
Issue number16
DOIs
StatePublished - 2016

Keywords

  • 4′-Thionucleosides
  • Anticancer
  • HSP90
  • Structure–activity relationship

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