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

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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 June 19, 2021, https://neomed.omeka.net/items/show/7656.

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