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

• 4-(2,3-Dichlorophenyl)piperazine-1-carboxylic acid was used as a lead compound, four mononuclear complexes were synthesized.
• Complexes were structurally determined by single-crystal X-ray diffraction.
• Telomerase inhibitory assay was consistent with the result of calculation.
• Antiproliferative activity was investigated in human cancer cell line HepG2.

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 ± 0.91 μM) 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 μM) for the complex 1 having good inhibitory activity against HepG2 was at the same micromolar concentrations with cis-platinum (2.2 ± 1.2 μM). While the IC50 value for the metal-free ligand, complex 2, 3 and 4 was more than 100 μM. 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.

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