Design, synthesis, and biological evaluation of 1, 3-disubstituted-pyrazole derivatives as new class I and IIb histone deacetylase inhibitors.
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.
Mesh Terms:
Antineoplastic Agents, Cell Proliferation, Cell Survival, Crystallography, X-Ray, Dose-Response Relationship, Drug, Drug Design, Drug Screening Assays, Antitumor, HeLa Cells, Histone Deacetylase 1, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Humans, K562 Cells, MCF-7 Cells, Models, Molecular, Molecular Structure, Pyrazoles, Structure-Activity Relationship, Tumor Cells, Cultured, U937 Cells
Antineoplastic Agents, Cell Proliferation, Cell Survival, Crystallography, X-Ray, Dose-Response Relationship, Drug, Drug Design, Drug Screening Assays, Antitumor, HeLa Cells, Histone Deacetylase 1, Histone Deacetylase 2, Histone Deacetylase Inhibitors, Humans, K562 Cells, MCF-7 Cells, Models, Molecular, Molecular Structure, Pyrazoles, Structure-Activity Relationship, Tumor Cells, Cultured, U937 Cells
Eur J Med Chem
Date: Oct. 30, 2014
PubMed ID: 25218912
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