Synthesis and structure-activity relationship of histone deacetylase (HDAC) inhibitors with triazole-linked cap group |
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Authors: | Chen Po C Patil Vishal Guerrant William Green Patience Oyelere Adegboyega K |
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Affiliation: | aSchool of Chemistry and Biochemistry, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA |
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Abstract: | Histone deacetylase (HDAC) inhibition is a recent, clinically validated therapeutic strategy for cancer treatment. Small molecule HDAC inhibitors identified so far fall in to three distinct structural motifs: the zinc-binding group (ZBG), a hydrophobic linker, and a recognition cap group. Here we report the suitability of a 1,2,3-triazole ring as a surface recognition cap group-linking moiety in suberoylanilide hydroxamic acid-like (SAHA-like) HDAC inhibitors. Using “click” chemistry (Huisgen cycloaddition reaction), several triazole-linked SAHA-like hydroxamates were synthesized. Structure–activity relationship revealed that the position of the triazole moiety as well as the identity of the cap group markedly affected the in vitro HDAC inhibition and cell growth inhibitory activities of this class of compounds. |
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Keywords: | Histone deacetylase (HDAC) Histone deacetylase-like protein (HDLP) Suberoylanilide hydroxamic acid (SAHA) Trichostatin A (TSA) Zinc-binding group (ZBG) SAHA-like hydroxamates, 1,2,3-triazole Click chemistry Molecular docking AutoDock |
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