title: Synthesis, activity evaluation, and docking analysis of barbituric acid aryl hydrazone derivatives as RSK2 inhibitors.
abstract: The 90 kDa ribosomal S6 kinases (RSKs), especially RSK2, have attracted attention for the development of new anticancer agents. Through structural optimization of the hit compound 1 from our previous study, a series of barbituric acid aryl hydrazone analogues were designed and synthesized as potential RSK2 inhibitors. The most potent one, compound 9, showed a higher activity against RSK2 with an IC50 value of 1.95 μM. To analyze and elucidate their structure-activity relationship, the homology model of RSK2 N-terminal kinase domain was built and molecular docking simulations were performed, which provide helpful clues to design new inhibitors with desired activities.
authors.affiliation: Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors.forename: Mengzhu
authors.initials: M
authors.lastname: Xue
authors.forename: Minghao
authors.initials: M
authors.lastname: Xu
authors.forename: Weiqiang
authors.initials: W
authors.lastname: Lu
authors.forename: Jin
authors.initials: J
authors.lastname: Huang
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
authors.forename: Yufang
authors.initials: Y
authors.lastname: Xu
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liu
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D001463:Barbiturates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D001463:Barbiturates; D006835:Hydrazones; D047428:Protein Kinase Inhibitors; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C032232:barbituric acid