title: Design, synthesis and antiproliferative activities of novel benzamides derivatives as HDAC inhibitors.
abstract: Guided by the principle of nonclassical electronic isosterism and structural optimization, a series of novel HDAC inhibitors bearing a bicyclic heterocycle moiety were designed and synthesized based on the lead compound of MS-275. All the prepared compounds were evaluated for their in vitro antiproliferative activities against HCT-116, MCF-7 and A549 human cancer cell lines, all compounds exerted excellent antitumor activities. Moreover, the compound 4a exhibited an acceptable pharmacokinetic profile with bio-availability in rat of 76% and could be considered as a candidate compound for further development.
authors.affiliation: Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yongzhen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China; Department of Medicinal Chemistry, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xie
authors.affiliation: Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China; Department of Medicinal Chemistry, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China; Department of Medicinal Chemistry, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China.
authors.forename: Pengyu
authors.initials: P
authors.lastname: Qian
authors.affiliation: Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
authors.forename: Yanjin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute of Radiation and Irradiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China; Department of Medicinal Chemistry, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China. Electronic address: lisx28@163.com.
authors.forename: Shuxin
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005260:Female; D045325:HCT116 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases
keywords: Acrylamide; Antiproliferative; Benzamides derivatives; HDAC; Pharmacokinetic; Synthesis