Synthesis and Anticancer Mechanism Investigation of Dual Hsp27 and Tubulin Inhibitors
Title
Synthesis and Anticancer Mechanism Investigation of Dual Hsp27 and Tubulin Inhibitors
Creator
Zhong B; Chennamaneni S; Lama R; Yi X; Geldenhuys W J; Pink J J; Dowlati A; Xu Y; Zhou A M; Su B
Publisher
Journal of Medicinal Chemistry
Date
2013
2013-07
Description
Heat shock protein 27 (Hsp27) is a chaperone protein, and its expression is increased in response to various stress stimuli including anticancer chemotherapy, which allows the cells to survive and causes drug resistance. We previously identified lead compounds that bound to Hsp27 and tubulin via proteomic approaches. Systematic ligand based optimization in the current study significantly increased the cell growth inhibition and apoptosis inducing activities of the compounds. Compared to the lead compounds, one of the new derivatives exhibited much better potency to inhibit tubulin polymerization but a decreased activity to inhibit Hsp27 chaperone function, suggesting that the structural modification dissected the dual targeting effects of the compound. The most potent compounds 20 and 22 exhibited strong cell proliferation inhibitory activities at subnanomolar concentration against 60 human cancer cell lines conducted by Developmental Therapeutic Program at the National Cancer Institute and represented promising candidates for anticancer drug development.
Subject
breast-cancer; c-dependent activation; cancer cells; chaperone activity; cytochrome-c; heat-shock proteins; in-vitro; nimesulide analog jcc76; pancreatic-cancer; Pharmacology & Pharmacy; self-association
Identifier
Format
Journal Article
URL Address
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Rights
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Pages
5306-5320
Issue
13
Volume
56
Citation
Zhong B; Chennamaneni S; Lama R; Yi X; Geldenhuys W J; Pink J J; Dowlati A; Xu Y; Zhou A M; Su B, “Synthesis and Anticancer Mechanism Investigation of Dual Hsp27 and Tubulin Inhibitors,” NEOMED Bibliography Database, accessed April 26, 2024, https://neomed.omeka.net/items/show/7656.