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 National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
- Files in This Item:
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