title: 5-aryl-1,3,4-thiadiazole-based hydroxamic acids as histone deacetylase inhibitors and antitumor agents: synthesis, bioevaluation and docking study.
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 hydroxamic acid) was approved by the FDA for the treatment of Tcell 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 analogues 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 IC50 values 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 5a and 5d displayed high affinities towards HDAC2 and 8.
authors.forename: Tran Thi Lan
authors.initials: TT
authors.lastname: Huong
authors.forename: Do Thi Mai
authors.initials: do TM
authors.lastname: Dung
authors.forename: Dao Thi Kim
authors.initials: DT
authors.lastname: Oanh
authors.forename: Tran Thi Bich
authors.initials: TT
authors.lastname: Lan
authors.forename: Phan Thi Phuong
authors.initials: PT
authors.lastname: Dung
authors.forename: Vu Duc
authors.initials: VD
authors.lastname: Loi
authors.forename: Kyung Rok
authors.initials: KR
authors.lastname: Kim
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Han
authors.forename: Jieun
authors.initials: J
authors.lastname: Yun
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Kang
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
authors.affiliation: Department of Pharmaceutical Chemistry, Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, Vietnam. namnh@hup.edu.vn.
authors.forename: Nguyen-Hai
authors.initials: NH
authors.lastname: Nam
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole; D006655:Histone Deacetylases