title: Synthesis and biological evaluation of novel histone deacetylases inhibitors with nitric oxide releasing activity.
abstract: A novel series of histone deacetylases inhibitors (HDACIs) containing benzofuroxan pharmacophore as nitric oxide (NO) donor were designed based on the combination principle and 'multifunctional drugs' theory. As a novel study on embedding NO donor into the structure of HDACIs, all designed hybrid compounds, especially 19d and 24d, displayed remarkable HDACs inhibitory activity and outstanding antiproliferative activity on tumor cells. Besides, they could produce high levels of NO in HCT-116 cells; furthermore, their antiproliferative activity on HCT-116 cells could be diminished by pretreatment with hemoglobin, as the NO scavenger, in a dose-dependent manner. All in all, our designed compounds displayed great inhibitory activities and might offer a prospective avenue to discover novel anti-cancer drugs.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, People's Republic of China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Duan
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, People's Republic of China.
authors.forename: Jinning
authors.initials: J
authors.lastname: Hou
authors.affiliation: Weifang Bochuang International Biological Medicinal Institute, Weifang, Shandong 261061, People's Republic of China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Chu
authors.affiliation: Color Ultrasonic Room, The People's Hospital of Shouguang, Weifang, Shandong 262700, People's Republic of China.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medical Chemistry, School of Pharmacy, Weifang Medical University, West Baotong Street, Weifang, Shandong 261053, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, People's Republic of China.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, People's Republic of China. Electronic address: zhangyingjie@sdu.edu.cn.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D001583:Benzoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006454:Hemoglobins / Q000037:antagonists & inhibitors / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D001583:Benzoxazoles; D006454:Hemoglobins; D056572:Histone Deacetylase Inhibitors; D010069:Oxadiazoles; D009569:Nitric Oxide; C014354:benzofuroxan; D006655:Histone Deacetylases
keywords: Benzofuroxan; Epigenetic; HDAC inhibitor; Multifunctional drugs; Nitric oxide