Design, synthesis, and anticancer activity of C8-substituted-4′-thionucleosides as potential HSP90 inhibitors. Issue 16 (15th August 2016)

• Record Type: Journal Article
• Authors: Qu, Shuhao; Mulamoottil, Varughese A.; Nayak, Akshata; Ryu, Seungyeon; Hou, Xiyan; Song, Jayoung; Yu, Jinha; Sahu, Pramod K.; Zhao, Long Xuan; Choi, Sun; Lee, Sang Kook; Jeong, Lak Shin
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 16(2016)
• Page Start: 3418
• Page End: 3428
• Publication Date: 2016-08-15
• Subjects: HSP90 -- 4′-Thionucleosides -- Structure–activity relationship -- Anticancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.05.041
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A series of C8-substituted-4′-thioadenosine analogs3a –3g, 15, and17 and their truncated derivatives4a –4j, 23 –25, and27 have been successfully synthesized fromd -ribose andd -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 derivatives15, 17, and27 exhibited potent anticancer activity, indicating that different mechanism of action might be involved in their biological activity.