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A ?-carboline derivative-based nickel(ii) complex as a potential antitumor agent: synthesis, characterization, and cytotoxicity.

ABSTRACT: A novel nickel(ii) complex of 6-methoxy-1-pyridine-?-carboline (4a) was synthesized and characterized. The cytotoxicities of the complex towards six cancer cell lines, including MGC-803, Hep G2, T24, OS-RC-2, NCI-H460, and SK-OV-3, and human normal liver cell line HL-7702 were investigated. The IC₅₀ values for MGC-803, Hep G2, T24, OS-RC-2, NCI-H460 and SK-OV-3 were generally in the micromolar range (3.77-15.10 ?M), lower than those of ligand 4 and cisplatin. Furthermore, 4a (6 ?M) significantly induced cell cycle arrest at the S phase, and caused the down-regulation of p-AKT, cyclin E, cyclin A and CDK2 and the up-regulation of p27. Various experiments showed that 4a induced apoptosis, activated caspase-3, increased the levels of reactive oxygen species (ROS) and enhanced the intracellular [Ca²⁺]_c levels in MGC-803. In addition, the expression of intrinsic apoptotic proteins, including cytochrome c and apaf-1, increased. Further intrinsic apoptosis was triggered via executive molecular caspase-9 and caspase-3. In short, 4a exerted its cytotoxic activity primarily through inducing cell cycle arrest at the S phase and intrinsic apoptosis.

SUBMITTER: Yang JM

PROVIDER: S-EPMC6072409 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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A β-carboline derivative-based nickel(ii) complex as a potential antitumor agent: synthesis, characterization, and cytotoxicity.

Yang Jing-Mei JM Zhu Yan-Hong YH Chen Sheng S Lu Xing X Wu Yi-Ming YM Ma Feng-E FE Li Liang-Ping LP Yang Yang Y Shi Zhen-Hao ZH Huang Kun-Yuan KY Hong Xue X Jiang Ping P Peng Yan Y

MedChemComm 20171124 1

A novel nickel(ii) complex of 6-methoxy-1-pyridine-β-carboline (4a) was synthesized and characterized. The cytotoxicities of the complex towards six cancer cell lines, including MGC-803, Hep G2, T24, OS-RC-2, NCI-H460, and SK-OV-3, and human normal liver cell line HL-7702 were investigated. The IC50 values for MGC-803, Hep G2, T24, OS-RC-2, NCI-H460 and SK-OV-3 were generally in the micromolar range (3.77-15.10 μM), lower than those of ligand 4 and cisplatin. Furthermore ...[more]

PMID: 30108903

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Project description:Interest is increasingly focused on the use of transition metal complexes as biochemical, medical, analytical, pharmaceutical, agronomic, anticancer, and antibacterial agents. In this study, three complexes of [Zn(H2L)Cl] (1), [Cu(H2L)(H2O)(NO3)] (2) and [Ni(H2L)(NO3)].2H2O (3) were synthesized from a 2-chloroquinoline-3-carbaldehyde derived ligand [H3L = ((E)-2-(((2-((2-hydroxyethyl)amino)quinolin-3-yl)methylene)amino)ethanol. The compounds were characterized using physicochemical and spectroscopic methods. The results demonstrate that the free ligand behaves as a tridentate ligand with one oxygen and two nitrogen (ONN) donor atoms in 1:1 metal:ligand ratio. The formation constants of the complexes were found to be (K Zn(II) = 2.3 × 106, K Cu(II) = 2.9 × 106, and K Ni(II) = 3.8 × 105). The thermodynamic parameters indicated that the reactions were spontaneous with exothermic nature of metal-ligand interaction energies. Based on the analyses of the experimental (EDX, FTIR, PXRD, MS and TGA) and DFT results, a distorted tetrahedral, a distorted square pyramidal and square planar geometry for Zn(II), Cu(II) and Ni(II) complexes, respectively, were proposed. The B3LYP calculated IR frequencies and TD-B3LYP calculated absorption spectra were found to be in good agreement with the corresponding experimental results. The powder XRD data confirmed that the Zn(II), Cu(II) and Ni(II) complexes have polycrystalline nature with average crystallite sizes of 27.86, 33.54, 37.40 Å, respectively. In vitro antibacterial activity analyses of the complexes were studied with disk diffusion method, in which the complexes showed better activity than the precursor ligand. Particularly the Cu(II) complex showed higher percent activity index (62, 90%), than both Zn(II) (54, 82%) and Ni(II) (41, 68%) complexes against both E. coli and P. aeruginosa, respectively. Using the DPPH assay, the complexes were further assessed for their antioxidant capacities. All metal complexes showed improved antioxidant activity than the free ligand. Zn(II) and Cu(II) complexes, which had IC50 values of 10.46 and 8.62 μg/ml, respectively, showed the best antioxidant activity. The calculated results of Lipinski's rule of five also showed that the target complexes have drug-like molecular nature and similarly, the results of binding mode of action of these compounds against E. coli DNA gyrase B and P. aeruginosa LasR.DNA were found to be in good agreement with the in vitro biological activities.

Dataset Information

A ?-carboline derivative-based nickel(ii) complex as a potential antitumor agent: synthesis, characterization, and cytotoxicity.

Publications

A β-carboline derivative-based nickel(ii) complex as a potential antitumor agent: synthesis, characterization, and cytotoxicity.

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