Synthesis and Biological Evaluation of Triazol-4-ylphenyl-Bearing Histone Deacetylase Inhibitors as Anticancer Agents

Journal of Medicinal Chemistry
2010.0

Abstract

Our triazole-based histone deacetylase inhibitor (HDACI), octanedioic acid hydroxyamide[3-(1-phenyl-1H-[1,2,3]triazol-4-yl)phenyl]amide (4a), suppresses pancreatic cancer cell growth in vitro with the lowest IC(50) value of 20 nM against MiaPaca-2 cell. In this study, we continued our efforts to develop triazol-4-ylphenyl bearing hydroxamate analogues by embellishing the terminal phenyl ring of 4a with different substituents. The isoform inhibitory profile of these hydroxamate analogues was similar to those of 4a. All of these triazol-4-ylphenyl bearing hydroxamates are pan-HDACIs like SAHA. Moreover, compounds 4h and 11a were found to be very effective inhibitors of cancer cell growth in the HupT3 (IC(50) = 50 nM) and MiaPaca-2 (IC(50) = 40 nM) cancer cell lines, respectively. Compound 4a was found to reactivate the expression of CDK inhibitor proteins and to suppress pancreatic cancer cell growth in vivo. Taken together, these data further support the value of the triazol-4-ylphenyl bearing hydroxamates in identifying potential pancreatic cancer therapies.

Knowledge Graph

Similar Paper

Synthesis and Biological Evaluation of Triazol-4-ylphenyl-Bearing Histone Deacetylase Inhibitors as Anticancer Agents
Journal of Medicinal Chemistry 2010.0
Design, synthesis, and evaluation of isoindolinone-hydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors
Bioorganic & Medicinal Chemistry Letters 2007.0
Design, synthesis, and evaluation of biphenyl-4-yl-acrylohydroxamic acid derivatives as histone deacetylase (HDAC) inhibitors
European Journal of Medicinal Chemistry 2009.0
A Series of Potent and Selective, Triazolylphenyl-Based Histone Deacetylases Inhibitors with Activity against Pancreatic Cancer Cells and Plasmodium falciparum
Journal of Medicinal Chemistry 2008.0
Design and synthesis of novel and highly-active pan-histone deacetylase (pan-HDAC) inhibitors
Bioorganic & Medicinal Chemistry 2014.0
Design, synthesis and biological evaluation of di-substituted cinnamic hydroxamic acids bearing urea/thiourea unit as potent histone deacetylase inhibitors
Bioorganic & Medicinal Chemistry Letters 2013.0
Development of Tetrahydroisoquinoline-Based Hydroxamic Acid Derivatives: Potent Histone Deacetylase Inhibitors with Marked in Vitro and in Vivo Antitumor Activities
Journal of Medicinal Chemistry 2011.0
1,3,4-Oxadiazole-Containing Histone Deacetylase Inhibitors: Anticancer Activities in Cancer Cells
Journal of Medicinal Chemistry 2014.0
Spirohydantoins and 1,2,4-triazole-3-carboxamide derivatives as inhibitors of histone deacetylase: Design, synthesis, and biological evaluation
European Journal of Medicinal Chemistry 2018.0
Design and synthesis of a new generation of substituted purine hydroxamate analogs as histone deacetylase inhibitors
Bioorganic & Medicinal Chemistry 2016.0