title: Synthesis, crystal structures, molecular docking, and in vitro biological activities of transition metals with 4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid.
abstract: Four novel mononuclear complexes, [Cd(L)2·2H2O] (1), [Ni(L)2·2H2O] (2) [Cu(L)2·H2O] (3), and [Zn(L)2·2H2O] (4) (CCDC numbers: 1444630-1444633 for complexes 1-4) (HL=4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid) were synthesized, and have been characterized by IR spectroscopy, elemental analysis, and X-ray crystallography. Molecular docking study preliminarily revealed that complex 1 had potential telomerase inhibitory activity. In accordance with the result of calculation, in vitro tests of the inhibitory activities of complex 1 against telomerase showed complex 1 (IC50=8.17±0.91μM) had better inhibitory activities, while complexes 2, 3 and 4 showed no inhibitory activities. Antiproliferative activity in human cancer cell line HepG2 was further determined by MTT assays. The IC50 value (6.5±0.2μM) for the complex 1 having good inhibitory activity against HepG2 was at the same micromolar concentrations with cis-platinum (2.2±1.2μM). While the IC50 value for the metal-free ligand, complex 2, 3 and 4 was more than 100μM. These results indicated that telomerase was potentially an anticancer drug target and showed that complex 1 was a potent inhibitor of human telomerase as well as an antiproliferative compound.
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, People's Republic of China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Yang
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, People's Republic of China.
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, People's Republic of China.
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Wu
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, People's Republic of China.
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Chen
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, People's Republic of China. Electronic address: sdutqss@163.com.
authors.forename: Shao-Song
authors.initials: SS
authors.lastname: Qian
authors.affiliation: School of Life Sciences, Shandong University of Technology, Zibo 255049, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D056945:Hep G2 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D028561:Transition Elements / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000621331:4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D010879:Piperazines; D028561:Transition Elements
keywords: Antiproliferative; Crystal structure; Metal complexes; Molecular docking; Telomerase inhibitor