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Synthesis and biological studies of copper(II) salicylaldehyde semicarbazone complexes with substituted pyridine ligands
Author
Teoh, You Chuan
Supervisor
Yan, Yaw Kai
Abstract
This dissertation reports the synthesis, characterization, DNA binding and cytotoxicity of (2,4-dihydroxybenzaldehyde dibenzyl semicarbazone) copper(II) (CuBz) complexes of substituted pyridines.
A series of substituted pyridines, (2-(4-morpholinyl) ethyl nicotinate (MEN), 2-(4-morpholinyl) ethyl isonicotinate (MEI), 2-(4-morpholinyl) ethyl nicotinamide, MEN and 2-(4-morpholinyl) ethyl isonicotinamide (MEIA), were prepared and used as ligands for the preparation of (2,4-dihydroxybenzaldehyde dibenzyl semicarbazone) copper(II) pyridine complexes. Four new copper(II) complexes, namely CuBz-MEN, CuBz-MEI, CuBz-MENA and CuBz-MEIA were prepared and characterized by elemental analysis and IR spectroscopy.
The ability of the copper(II) pyridine complexes to bind to different oligonucleotides was evaluated using the Fluorescence Intercalator Displacement (FID) assay. The binding affinity of the synthesized compounds was tested using one duplex-forming sequence, ds26 and two quadruplex-forming sequences from human telomeres (HTelo) and the c-myc promoter region, respectively. The synthesized compounds demonstrated good binding affinity (DC50 < 1.5 µM) and selectivity (average about 8-fold more selective) for HTelo over c- myc and ds26.
In addition, the synthesized compounds were screened for their cytotoxicity against the human leukaemia (MOLT-4) and breast cancer (MCF-7) cell lines via colorimetric MTT assay. The compounds showed relatively high cytotoxicity against MOLT-4 with IC50 values in the low micromolar range of 6-10 µM. However, the compounds were less cytotoxic against MCF-7, with IC50 values of 50-57 µM. Of all the copper(II) complexes, CuBz-MEIA was the most cytotoxic when tested against the MOLT-4 cell line (IC50 = 6.24 µM).
A series of substituted pyridines, (2-(4-morpholinyl) ethyl nicotinate (MEN), 2-(4-morpholinyl) ethyl isonicotinate (MEI), 2-(4-morpholinyl) ethyl nicotinamide, MEN and 2-(4-morpholinyl) ethyl isonicotinamide (MEIA), were prepared and used as ligands for the preparation of (2,4-dihydroxybenzaldehyde dibenzyl semicarbazone) copper(II) pyridine complexes. Four new copper(II) complexes, namely CuBz-MEN, CuBz-MEI, CuBz-MENA and CuBz-MEIA were prepared and characterized by elemental analysis and IR spectroscopy.
The ability of the copper(II) pyridine complexes to bind to different oligonucleotides was evaluated using the Fluorescence Intercalator Displacement (FID) assay. The binding affinity of the synthesized compounds was tested using one duplex-forming sequence, ds26 and two quadruplex-forming sequences from human telomeres (HTelo) and the c-myc promoter region, respectively. The synthesized compounds demonstrated good binding affinity (DC50 < 1.5 µM) and selectivity (average about 8-fold more selective) for HTelo over c- myc and ds26.
In addition, the synthesized compounds were screened for their cytotoxicity against the human leukaemia (MOLT-4) and breast cancer (MCF-7) cell lines via colorimetric MTT assay. The compounds showed relatively high cytotoxicity against MOLT-4 with IC50 values in the low micromolar range of 6-10 µM. However, the compounds were less cytotoxic against MCF-7, with IC50 values of 50-57 µM. Of all the copper(II) complexes, CuBz-MEIA was the most cytotoxic when tested against the MOLT-4 cell line (IC50 = 6.24 µM).
Date Issued
2018
Call Number
QD412.C1 Teo
Date Submitted
2018