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

doi:10.1016/j.bmc.2016.05.041

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

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

12 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 language	English
Pages (from-to)	3418-3428
Number of pages	11
Journal	Bioorganic and Medicinal Chemistry
Volume	24
Issue number	16
DOIs	https://doi.org/10.1016/j.bmc.2016.05.041
State	Published - 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Ltd

Keywords

4′-Thionucleosides
Anticancer
HSP90
Structure–activity relationship

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10.1016/j.bmc.2016.05.041

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@article{d4cf7b0c4eaa4f8cb0a6e548522c4788,

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

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 Vorbr{\"u}ggen 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.",

keywords = "4′-Thionucleosides, Anticancer, HSP90, Structure–activity relationship",

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

note = "Publisher Copyright: {\textcopyright} 2016 Elsevier Ltd",

year = "2016",

doi = "10.1016/j.bmc.2016.05.041",

language = "English",

volume = "24",

pages = "3418--3428",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

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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

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

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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 -

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

Abstract

Bibliographical note

Keywords

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