title: Design, synthesis and biological evaluation of isoquinoline-based derivatives as novel histone deacetylase inhibitors.
abstract: The design, synthesis and biological evaluation of a series of isoquinoline-based hydroxamic acid compounds as novel HDACs inhibitors were reported herein. A detailed SAR study showed most of the compounds displayed good to excellent inhibitory activities against HDAC1, 3, 6. The IC50 values of compound 10 c against HDAC1, 3, 6 were 4.17 ± 0.11 nM, 4.00 ± 0.10 nM, 3.77 ± 0.07 nM, respectively. Most of the compounds showed great anti-proliferative activities against RPMI 8226, HCT 116 and Hep G2 cells. The IC50 values of compounds 10 a-h against RPMI 8226 cancer cell proliferation were all below 1 μM. HCT 116 cell was sensitive to the compounds 10 a, 10 f-g and 18 a with the IC50 values <0.3 μM. The active compounds 10a-d did not show inhibitory activity against hERG channel. All these evidence indicated these compounds had great potential as HDACs inhibitors for the further development.
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; East China Normal University, Institutes for Advanced Interdisciplinary Research, North Zhongshan Road Campus: 3663 N. Zhongshan Rd., Shanghai 200062, PR China.
authors.forename: Lixuan
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wu
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Mingbo
authors.initials: M
authors.lastname: Su
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Mingyue
authors.initials: M
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zang
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China; East China Normal University, Institutes for Advanced Interdisciplinary Research, North Zhongshan Road Campus: 3663 N. Zhongshan Rd., Shanghai 200062, PR China. Electronic address: jli@mail.shcnc.ac.cn.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, PR China. Electronic address: hliu@mail.shcnc.ac.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
mesh_terms: D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis*; D006877:Hydroxamic Acids / Q000737:chemistry*; D007546:Isoquinolines / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007546:Isoquinolines; C039109:isoquinoline
keywords: HDACs; HDACs inhibitor; Hydroxamic acid; Isoquinoline