Synthesis, crystal structures, molecular docking, and in vitro biological activities of transition metals with 4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid

Four novel mononuclear complexes, [Cd(L)(2)center dot 2H(2)O] (1), [Ni(L)(2)center dot 2H(2)O] (2) [Cu(L)(2)center dot H2O] (3), and [Zn(L)(2)center dot 2H(2)O] (4) (CCDC number: 1444630-1444633 for complex 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 complexes 1 against telomerase showed complex 1 (IC50 = 8.17 +/- 0.91 mu M) 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 +/- 0.2 mu M) for the complex 1 having good inhibitory activity against HepG2 was at the same micromolar concentrations with cis-platinum (2.2 +/- 1.2 mu M). While the IC50 value for the metal-free ligand, complex 2, 3 and 4 was more than 100 mu M. 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. (C) 2016 Elsevier Ltd. All rights reserved.