title: Hybrids of the Benzofuran Core from Natural Products and the 2,4-Dihydroxy-5-isopropylbenzene Fragment as Potent Hsp90 Inhibitors: Design, Synthesis and Bioevaluation.
abstract: 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.
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P. R. China tel/fax: +86 025 83271216; +86 025 83271351.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Jian-Min
authors.initials: JM
authors.lastname: Jia
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P. R. China tel/fax: +86 025 83271216; +86 025 83271351.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P. R. China tel/fax: +86 025 83271216; +86 025 83271351.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Xu
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P. R. China tel/fax: +86 025 83271216; +86 025 83271351.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Guo
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P. R. China tel/fax: +86 025 83271216; +86 025 83271351.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P. R. China tel/fax: +86 025 83271216; +86 025 83271351.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Hao-Zhe
authors.initials: HZ
authors.lastname: Huang
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P. R. China tel/fax: +86 025 83271216; +86 025 83271351.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P. R. China tel/fax: +86 025 83271216; +86 025 83271351.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China.
authors.forename: Bahidja
authors.initials: B
authors.lastname: Cherfaoui
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P. R. China tel/fax: +86 025 83271216; +86 025 83271351. sunhaopeng@163.com.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China. sunhaopeng@163.com.|Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, P. R. China. sunhaopeng@163.com.
authors.forename: Hao-Peng
authors.initials: HP
authors.lastname: Sun
authors.affiliation: Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, P. R. China tel/fax: +86 025 83271216; +86 025 83271351. youqidong@gmail.com.|State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, P. R. China. youqidong@gmail.com.
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: You
keywords: 2,4-Dihydroxy-5-isopropylbenzene; Benzofuran; Hsp90 inhibitor; Hybrid; Molecular design