5-Aryl-1,3,4-thiadiazole-based Hydroxamic Acids as Histone Deacetylase Inhibitors and Antitumor Agents: Synthesis, Bioevaluation and Docking Study

5-Aryl-1,3,4-thiadiazole-based Hydroxamic Acids as Histone Deacetylase Inhibitors and Antitumor Agents: Synthesis, Bioevaluation and Docking Study

tháng 8 17, 2017

Title:	5-Aryl-1,3,4-thiadiazole-based Hydroxamic Acids as Histone Deacetylase Inhibitors and Antitumor Agents: Synthesis, Bioevaluation and Docking Study
Authors:	Vu, Duc Loi
Keywords:	Histone deacetylase (HDAC) inhibitors;5-aryl-1,3,4-thiadiazole;cytotoxicity;heterocycle.
Issue Date:	2014
Publisher:	Bentham Science Publishers
Abstract:	The search for newer histone deacetylase (HDAC) inhibitors has attracted a great deal of interest of medicinal chemists worldwide, especially after the first HDAC inhibitor (Zolinza ® , widely known as SAHA or Suberoylanilide hy-droxamic acid) was approved by the FDA for the treatment of T-cell lymphoma in 2006. As a continuity of our ongoing research in this area, we designed and synthesized a series of 5-aryl-1,3,4-thiadiazole-based hydroxamic acids as ana-logues of SAHA and evaluated their biological activities. Most of the compounds in this series, e.g.compounds with 5-aryl moiety being 2-furfuryl (5a), 5-bromofuran-2-yl (5b), 5-methylfuran-2-yl (5c), thiophen-2-yl (5d), 5-methylthiophen-2-yl (5f) and pyridyl (5g-i), were found to have potent anticancer cytotoxicity with IC50values of generally 5- to 10-fold lower than that of SAHA in 4 human cancer cell lines assayed. Those compounds with potent cytotoxicity were also found to have strong HDAC inhibition effects. Docking studies revealed that compounds 5aand 5ddisplayed high affini-ties towards HDAC2 and 8.
URI:	http://repository.vnu.edu.vn/handle/VNU_123/11433
ISSN:	0223-5234
Appears in Collections:	SMP - Papers / Tham luận HN-HT

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