Design, synthesis and preliminary biological evaluation of indoline-2,3-dione derivatives as novel HDAC inhibitors

Kang Jin; Shanshan Li; Xiaoguang Li; Jian Zhang; Wenfang Xu; Xuechen Li

doi:10.1016/j.bmc.2015.05.048

Design, synthesis and preliminary biological evaluation of indoline-2,3-dione derivatives as novel HDAC inhibitors

Bioorg Med Chem. 2015 Aug 1;23(15):4728-4736. doi: 10.1016/j.bmc.2015.05.048. Epub 2015 Jun 3.

Authors

Kang Jin¹, Shanshan Li¹, Xiaoguang Li¹, Jian Zhang¹, Wenfang Xu², Xuechen Li³

Affiliations

¹ Department of Medicinal Chemistry, School of Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China.
² Department of Medicinal Chemistry, School of Pharmacy, School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, Jinan, Shandong 250012, PR China. Electronic address: wfxu@yahoo.cn.
³ Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, PR China. Electronic address: xuechenl@hku.hk.

PMID: 26100440
DOI: 10.1016/j.bmc.2015.05.048

Abstract

Histone deacetylases (HDACs) are zinc-dependent or NAD(+) dependent enzymes and play a critical role in the process of tumor development. Herein a series of indoline-2,3-dione derivatives have been designed and synthesized as potential HDACs inhibitors. The preliminary biological evaluation showed that most compounds synthesized have exhibited moderate Hela cell nuclear extract inhibitory activities, among which compound 25a (IC50=10.13 nM) has shown the best efficacy. The anti-proliferative activities of some of these compounds were also discussed.

Keywords: Biological evaluation; HDAC inhibitors; Indoline-2,3-dione derivatives; QSAR; Synthesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / pharmacology
Antineoplastic Agents / therapeutic use
Binding Sites
Cell Proliferation / drug effects
Drug Design*
Drug Screening Assays, Antitumor
HeLa Cells
Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
Heterocyclic Compounds, 4 or More Rings / pharmacology
Heterocyclic Compounds, 4 or More Rings / therapeutic use
Histone Deacetylase Inhibitors / chemical synthesis*
Histone Deacetylase Inhibitors / pharmacology
Histone Deacetylase Inhibitors / therapeutic use
Histone Deacetylases / chemistry
Histone Deacetylases / metabolism
Humans
Indoles / chemistry*
Indoles / pharmacology
Indoles / therapeutic use
Liver Neoplasms / drug therapy
Liver Neoplasms / pathology
Mice
Mice, Nude
Molecular Docking Simulation
Protein Structure, Tertiary
Quantitative Structure-Activity Relationship
Spiro Compounds / chemical synthesis*
Spiro Compounds / pharmacology
Spiro Compounds / therapeutic use
Transplantation, Heterologous

Substances

4-(3-(5'-bromo-2'-oxospiro((1,3)dioxane-2,3'-indoline)-1'-yl)propanamido)-N-hydroxybenzamide
Antineoplastic Agents
Heterocyclic Compounds, 4 or More Rings
Histone Deacetylase Inhibitors
Indoles
Spiro Compounds
indoline-2,3-dione
Histone Deacetylases