2. Academic Validation
  3. Design, synthesis, and anticancer activity of C8-substituted-4'-thionucleosides as potential HSP90 inhibitors

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

  • Bioorg Med Chem. 2016 Aug 15;24(16):3418-28. doi: 10.1016/j.bmc.2016.05.041.
Shuhao Qu 1,  Varughese A Mulamoottil 2,  Akshata Nayak 2,  Seungyeon Ryu 2,  Xiyan Hou 3,  Jayoung Song 4,  Jinha Yu 4,  Pramod K Sahu 4,  Long Xuan Zhao 5,  Sun Choi 2,  Sang Kook Lee 4,  Lak Shin Jeong 6
Affiliations

Affiliations

  • 1 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea; College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
  • 2 College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea.
  • 3 College of Life Science, Dalian Nationalities University, Dalian 116600, China.
  • 4 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.
  • 5 College of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian 116-029, China.
  • 6 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: lakjeong@snu.ac.kr.
PMID: 27283788 DOI: 10.1016/j.bmc.2016.05.041
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 100μM. 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.

Keywords

4′-Thionucleosides; Anticancer; HSP90; Structure–activity relationship.

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