Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Investigation of B, C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors for use as anti-breast cancer agents

Authors
Kim, Ho ShinVan-Hai HoangHong, MannkyuKim, Kyung ChulAnn, JihyaeCong-Truong NguyenSeo, Ji HaeChoi, HoonKim, Jun YongKim, Kyu-WonByun, Woong SubLee, SangkookLee, SeungbeomSuh, Young-GerChen, JiePark, Hyun-JuCho, Tae-MinKim, Ji YoungSeo, Jae HongLee, Jeewoo
Issue Date
1-4월-2019
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Keywords
Heat shock protein 90; HSP90; Hypoxia Inducible Factor-1a; HIF-1 alpha; Antitumor; Breast cancer; Deguelin
Citation
BIOORGANIC & MEDICINAL CHEMISTRY, v.27, no.7, pp.1370 - 1381
Indexed
SCIE
SCOPUS
Journal Title
BIOORGANIC & MEDICINAL CHEMISTRY
Volume
27
Number
7
Start Page
1370
End Page
1381
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/66081
DOI
10.1016/j.bmc.2019.02.040
ISSN
0968-0896
Abstract
On the basis of deguelin, a series of the B, C-ring truncated surrogates with N-substituted amide linkers were investigated as HSP90 inhibitors. The structure activity relationship of the template was studied by incorporating various substitutions on the nitrogen of the amide linker and examining their HIF-1 alpha inhibition. Among them, compound 57 showed potent HIF-1 alpha inhibition and cytotoxicity in triple-negative breast cancer lines in a dose-dependent manner. Compound 57 downregulated expression and phosphorylation of major client proteins of HSP90 including AKT, ERK and STAT3, indicating that its antitumor activity was derived from the inhibition of HSP90 function. The molecular modeling of 57 demonstrated that 57 bound well to the C-terminal ATP-binding pocket in the open conformation of the hHSP90 homodimer with hydrogen bonding and pi-cation interactions. Overall, compound 57 is a potential antitumor agent for triple-negative breast cancer as a HSP90 Cterminal inhibitor.
Files in This Item
There are no files associated with this item.
Appears in
Collections
Graduate School > Department of Biomedical Sciences > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Seo, Jae Hong photo

Seo, Jae Hong
의과학과
Read more

Altmetrics

Total Views & Downloads

BROWSE