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Hybrids of the Benzofuran Core from Natural Products and the 2,4‐Dihydroxy‐5‐isopropylbenzene Fragment as Potent Hsp90 Inhibitors: Design, Synthesis and Bioevaluation
Author(s) -
Jia JianMin,
Liu Fang,
Xu XiaoLi,
Guo XiaoKe,
Jiang Fen,
Huang HaoZhe,
Pan Yang,
Cherfaoui Bahidja,
Sun HaoPeng,
You QiDong
Publication year - 2014
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.201300182
Subject(s) - benzofuran , chemistry , hsp90 , rational design , combinatorial chemistry , hsp90 inhibitor , drug discovery , stereochemistry , enzyme , computational biology , biochemistry , biology , gene , genetics , heat shock protein
Several chemical fragments have been confirmed as highly efficient cores for the design of Hsp90 inhibitors. Molecular hybridization of potent fragments has been widely used as a rational drug discovery strategy. In this study, a novel class of hybrids of benzofuran, a privileged core from natural products, and 2,4‐dihydroxy‐5‐isopropyl phenyl, an efficient fragment in Hsp90 inhibitors, were designed and synthesized. Subsequent evaluation confirmed they inhibited cell proliferation and regulated the level of client proteins through Hsp90 inhibition. Some of the hybrids can serve as leads to obtain novel chemotypes of Hsp90 inhibitors. The methods reported here may expand the range of known structural types accommodated by the ATP binding site of Hsp90.