%0 Journal Article %A Pugh, Kyler W. %A Zhang, Zheng %A Wang, Jian %A Xu, Xiuzhi %A Munthali, Vitumbiko %A Zuo, Ang %A Blagg, Brian S. J. %D 2020 %T From Bacteria to Cancer: A Benzothiazole-Based DNA Gyrase B Inhibitor Redesigned for Hsp90 C‑Terminal Inhibition %U https://acs.figshare.com/articles/journal_contribution/From_Bacteria_to_Cancer_A_Benzothiazole-Based_DNA_Gyrase_B_Inhibitor_Redesigned_for_Hsp90_C_Terminal_Inhibition/12593897 %R 10.1021/acsmedchemlett.0c00100.s001 %2 https://acs.figshare.com/ndownloader/files/23581289 %K DNA gyrase B inhibitor %K MCF -7 %K DNA gyrase B %K Hsp 90 C-terminal inhibitors %K HSR %K client proteins %K Hsp 90 C-terminal inhibition %K benzothiazole-based scaffold %K micromolar activity %K heat shock response %K Benzothiazole-Based DNA Gyrase B In... %K Hsp 90 C-terminal inhibitor %K Several compounds %K anticancer effects %K SKBr 3 breast cancer cell lines %K Hsp 90 N-terminal pan inhibitors %X Heat shock protein 90 (Hsp90) is a molecular chaperone that is responsible for the folding and maturation of client proteins that are associated with all ten hallmarks of cancer. Hsp90 N-terminal pan inhibitors have experienced unfavorable results in clinical trials due to induction of the heat shock response (HSR), among other concerns. Novobiocin, a well characterized DNA gyrase B inhibitor, was identified as the first Hsp90 C-terminal inhibitor that manifested anticancer effects without induction of the HSR. In this letter, a library of Hsp90 C-terminal inhibitors derived from a benzothiazole-based scaffold, known to inhibit DNA gyrase B, was designed, synthesized, and evaluated. Several compounds were found to manifest low micromolar activity against both MCF-7 and SKBr3 breast cancer cell lines via Hsp90 C-terminal inhibition. %I ACS Publications