Identification of vibsanin A analog as a novel HSP90 inhibitor. Issue 2 (15th January 2020)

• Record Type: Journal Article
• Authors: Miura, Kazuki; Matsuki, Wataru; Ogura, Akihiro; Takao, Ken-ichi; Simizu, Siro
• Is Part Of: Bioorganic & medicinal chemistry. Volume 28:Issue 2(2020)
• Publication Date: 2020-01-15
• Subjects: Vibsanin A -- Natural product -- Anti-cancer activity -- HSP90 inhibitor; 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.2019.115253
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Vibsanin A is the first natural product isolated from Viburnum awabuki and has several biological activities. We have reported that a vibsanin A analog, obtained from process of total synthesis of vibsanin A, has anti-proliferative activity against human cancer cell lines. In this study, we evaluated anti-proliferative effect of the vibsanin A analogs against various human cancer cell lines and examined molecular target of the analog in human cells. Among the vibsanin A analogs, vibsanin A analog C (VAC) showed anti-proliferative effect against various cancer cell lines, and the anti-proliferative activity was strongest among the vibsanin A analogs. Additionally, VAC fluctuated amounts of HSP90-related proteins in cells and inhibited HSP90-mediated protein refolding of luciferase in vitro . These results suggest that the anti-proliferative activity of VAC is due to HSP90 inhibition, and VAC has a potential as novel anti-cancer drug as HSP90 inhibitor.