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Int. J. Mol. Sci. 2019, 20(4), 945;

Hydroxamic Acid-Based Histone Deacetylase (HDAC) Inhibitors Bearing a Pyrazole Scaffold and a Cinnamoyl Linker

Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy
Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, University of Messina, Viale F. Stagno D’Alcontres 31, 98166 Messina, Italy
Higher Institute of Applied Sciences and Technology of Mahdia, University of Monastir, Sidi Massa-oud, Hiboun Mahdia Tunisian 5100, Tunisia
Consorzio Interuniversitario Nazionale di ricerca in Metodologie e Processi Innovativi di Sintesi (C.I.N.M.P.S.), Via E. Orabona, 4, 70125 Bari, Italy
Author to whom correspondence should be addressed.
Received: 31 January 2019 / Revised: 15 February 2019 / Accepted: 18 February 2019 / Published: 21 February 2019
(This article belongs to the Special Issue Histone Deacetylase Inhibitors in Health and Disease)
PDF [2265 KB, uploaded 23 February 2019]


Genetic abnormalities have been conventionally considered as hallmarks of cancer. However, recent studies have demonstrated that epigenetic mechanisms are also implicated in the insurgence and development of cancer. Patterns of the epigenetic component include DNA methylation and histone modifications. Acetylation of histones is controlled by histone acetyltransferases (HATs) and histone deacetylases (HDACs). Imbalance of these two enzymatic systems is known to be a key factor in tumor progression. Because HDACs have been found to function incorrectly in cancer, various HDAC inhibitors (HDACIs) are being investigated to act as cancer chemotherapeutics. Herein, we report the synthesis, docking studies and biological activity of a series of hydroxamic acid-based HDACIs bearing an N1-aryl or N1-H pyrazole nucleus as surface recognition motif and a cinnamoyl group as a linker to the hydroxamic acid zinc-binding group (ZBG). Some of the tested compounds exhibited inhibitory properties towards HDACs and antiproliferative activity against neuroblastoma SH-SY5Y tumor cell line both at micromolar concentrations. View Full-Text
Keywords: HDAC inhibitors; hydroxamic acid; N1-aryl-pyrazole; N1-H-pyrazole; antiproliferative activity HDAC inhibitors; hydroxamic acid; N1-aryl-pyrazole; N1-H-pyrazole; antiproliferative activity

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Zagni, C.; Citarella, A.; Oussama, M.; Rescifina, A.; Maugeri, A.; Navarra, M.; Scala, A.; Piperno, A.; Micale, N. Hydroxamic Acid-Based Histone Deacetylase (HDAC) Inhibitors Bearing a Pyrazole Scaffold and a Cinnamoyl Linker. Int. J. Mol. Sci. 2019, 20, 945.

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