title: Discovery of a cobalt complex with high MEK1 binding affinity.
abstract: A series of Schiff base ligands (L1-L5) and their cobalt(II) complexes (1-5) were designed and synthesized for MEK1 binding experiment. The biological evaluation results showed that Bis(N,N'-disalicylidene)-3,4-phenylenediamine-cobalt(II) 1 and Bis(N,N'-disalicylidene)-1,2-cyclohexanediamine-cobalt(II) 2 are much more effective than the parent Schiff bases (L1and L2). Importantly, 2 exhibited MEK1 binding affinity with IC5071nM, which is so far the best result for metal complexes and more potent than U0126 (7.02μM) and AZD6244 (2.20μM). Docking study was used to elucidate the binding modes of complex 2 with MEK1. Thus cobalt(II) complex 2 may be further developed as a novel MEK1 inhibitor.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Tongliang
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China. Electronic address: pingxu@bjmu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
mesh_terms: D001665:Binding Sites; D003035:Cobalt / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D003514:Cyclohexylamines / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D020128:Inhibitory Concentration 50; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012545:Schiff Bases / Q000737:chemistry
chemical_list: D056831:Coordination Complexes; D003514:Cyclohexylamines; D047428:Protein Kinase Inhibitors; D012545:Schiff Bases; D003035:Cobalt; C030435:1,2-cyclohexanediamine; D048369:MAP Kinase Kinase 1
keywords: Cobalt complex; Docking; Kinase; MEK; Schiff base