Synthesis, bioevaluation and docking study of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents

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Title
Synthesis, bioevaluation and docking study of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents
Author(s)
N H Nam; T L Huong; D T M Dung; P T P Dung; D T K Oanh; S H Park; K Kim; B W Han; Ji Eun Yun; Jong Soon Kang; Y Kim; S B Han
Bibliographic Citation
Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 29, no. 5, pp. 611-618
Publication Year
2014
Abstract
Since the first histone deacetylase (HDAC) inhibitor (Zolinza®, widely known as suberoylanilide hydroxamic acid; SAHA) was approved by the Food and Drug Administration for the treatment of T-cell lymphoma in 2006, the search for newer HDAC inhibitors has attracted a great deal of interest of medicinal chemists worldwide. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-substitutedphenyl-1,3,4-thiadiazole-based hydroxamic acids as analogues of SAHA and evaluated their biological activities. A number of compounds in this series, for example, N1-hydroxy-N8-(5-(2-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5b), N1-hydroxy-N8-(5-(3-chlorophenyl-1,3,4-thiadiazol-2-yl)octandiamide (5c) and N1-hydroxy-N8-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)octandiamide (5d), were found to possess potent anticancer cytotoxicity and HDAC inhibition effects. Compounds 5b-d were generally two- to five-fold more potent in terms of cytotoxicity compared to SAHA against five cancer cell lines tested. Docking studies revealed that these hydroxamic acid displayed higher affinities than SAHA toward HDAC8
Keyword
5-phenyl-1,3,4-thiadiazoleCytotoxicityHeterocycleHistone deacetylase (HDAC) inhibitors
ISSN
1475-6366
Publisher
T&F (Taylor & Francis)
DOI
http://dx.doi.org/10.3109/14756366.2013.832238
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of Bioinfrastructure > Laboratory Animal Resource Center > 1. Journal Articles
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