title: Design, synthesis, and biological evaluation of 1, 3-disubstituted-pyrazole derivatives as new class I and IIb histone deacetylase inhibitors.
abstract: A novel series of HDAC inhibitors demonstrating class I and IIb subtype selectivity have been identified using a scaffold-hopping strategy. Several designed compounds showed better selectivity for class I and IIb over class IIa HDAC isoforms comparing to the FDA approved HDAC targeting drug SAHA. A representative lead compound 22 bearing a biphenyl moiety demonstrated promising class I and IIb HDAC isoforms selectivity and in vitro anticancer activities against several cancer cell lines. This work could serve as a fundamental platform for further exploration of selective HDAC inhibitors using designed molecular scaffold.
authors.affiliation: Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Yao
authors.affiliation: School of Medical Engineering, Hefei University of Technology, Hefei, Anhui 230009, China.
authors.forename: Chenzhong
authors.initials: C
authors.lastname: Liao
authors.affiliation: The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Liu
authors.affiliation: School of Medical Engineering, Hefei University of Technology, Hefei, Anhui 230009, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: tu_zhengchao@gibh.ac.cn.
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China. Electronic address: jiang_sheng@gibh.ac.cn.
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D011720:Pyrazoles; C031280:pyrazole; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
keywords: HDAC; Isoforms selectivity; Scaffold-hopping; Structure–activity relationship