TY - JOUR
T1 - Design, synthesis, and anticancer activity of C8-substituted-4′-thionucleosides as potential HSP90 inhibitors
AU - Qu, Shuhao
AU - Mulamoottil, Varughese A.
AU - Nayak, Akshata
AU - Ryu, Seungyeon
AU - Hou, Xiyan
AU - Song, Jayoung
AU - Yu, Jinha
AU - Sahu, Pramod K.
AU - Zhao, Long Xuan
AU - Choi, Sun
AU - Lee, Sang Kook
AU - Jeong, Lak Shin
N1 - Funding Information:
This research was supported by grants from Mid-career Research Program (370C-20130120) through the Ministry of Education, Science and Technology (MEST) and the National Research Foundation , Korea and the R&D Convergence Center Support Program of the Ministry of Agriculture, Food and Rural Affairs , Korea.
Publisher Copyright:
© 2016 Elsevier Ltd
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - 4′-Thionucleosides
KW - Anticancer
KW - HSP90
KW - Structure–activity relationship
UR - http://www.scopus.com/inward/record.url?scp=84978393985&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2016.05.041
DO - 10.1016/j.bmc.2016.05.041
M3 - Article
C2 - 27283788
AN - SCOPUS:84978393985
SN - 0968-0896
VL - 24
SP - 3418
EP - 3428
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
IS - 16
ER -