Complex compounds are made up of a central metal ion with one or more ligands. Complex compounds continue to be developed in the field of medicine. Cis-platin, a complex compound used as the first anticancer drug, experienced rapid development in the 1960s. However, platinum-based complexes cause side effects at certain doses and provide drug resistance during the therapeutic process. It triggered the development and discovery of new non-platinum based complex compounds. One of the transition metals used in the synthesis of anticancer complex compounds is Cu (II). Cu(II) is an essential element and plays an important role in the human body as a constituent of redox enzymes and hemocyanin. Therefore, Cu(II) metal is expected to have good anticancer activity capabilities. Previous research has shown the effectiveness of imidazole-based complex compounds and their derivatives in countering and showing cytotoxic effects on cancer cells. Nitrogen atoms, as donor electron pairs, can form complex compounds with metals. The effectiveness of these compounds in fighting cancer is related to their interaction with DNA. Other nitrogen atoms contained in complex compounds can interact non-covalently. The positive charge of metals can be involved in electrostatic interactions with the negative charge of the sugar-phosphate group on DNA. For this reason, complex compounds of Cu (II) metal ions made with 2,4,5-triphenyl-1H-imidazole ligands in this study were tested for anticancer activity by MTT method in vitro against breast cancer cells (T74D cells) and cervix cancer cells (HeLa cells).
In this research, the complex compound which has been obtained is in the form of a solid needle and contains 72.127% of complex Cu (II) -2.4,5-triphenyl-1 H- imidazole. The maximum wavelengths of the 2,4,5-triphenyl-1 H -imidazole ligand and the complex Cu (II) -2,4,5-triphenyl-1 H -imidazole are 243 nm and 529 nm, respectively. The increase in maximum wavelength changes is caused by the electron transition d-d which results in the transfer of charge from the metal to the ligand. These data support previous research which showed that the maximum wavelength of the complex Cu (II) -arylazoimidazole shifted toward a larger wave compared to the 2,4,5-triphenyl-1 H -imidazole ligand.
The new peak in FTIR spectroscopy appears at wave number 422.38 cm -1 . In accordance with previous studies which showed the peak bond of metal and ligand (Cu-N) appeared at wave 453 cm -1 , whereas in H 2 O ligand appeared at 534.25 cm-1 indicating the presence of Cu-O vibrations. Thermogravimetric analysis of Cu (II) -2,4,5-triphenyl-1 H -imidazole was carried out at 25-600 ° C with a complex sample weight of 6.3670 mg. At TGA there was a decomposition stage. Weight reduction of 86.8791% occurred at 255.33-355.83 ° C indicating complex decomposition consisting of 2 2,4,4-triphenyl-1 H -imidazole ligand molecules, 2 H 2 O molecules and 1 Cl 2 molecules. This is consistent with the theory in which the 86.8791% weight reduction is a decomposition (C 21 H 16 N 2 ) 2 (H 2 O) 2 Cl 2 ). A residual of 13,1209% is predicted as Cu, as mentioned in a study which showed that CuO is the final residue of the complex [Cu (6-hydroxyphicholine) 2 (3-picolinate) 2 ] .
The cytotoxicity test was carried out by the MTT method (3- (4,5-dimethyltiazole-2-yl) 2,5-diphenyltetrazolium bromide) using T74D breast cancer cells and HeLa cervical cancer cells and based on the MTT complex Cu (II) -2 test curve , 4,5-triphenyl-1 H- imidazole. The CC 50 value of Cu (II) complex -2,4,5-triphenyl-1 H -imidazole was 8.78 µg / ml for T74D breast cancer cells and 14.46 µg / ml for HeLa cervical cancer cells, with P> 0 .5. The compound added to Vero cells showed a cytotoxic effect at CC 50 = 44.74 μg / ml. One percent DMSO (negative control) showed no cytotoxic effects on Vero cells. At high concentrations of complex Cu (II) -2,4,5-triphenyl-1 H -imidazole, more T74D breast cancer cells and HeLa cervical cancer cells die. In high concentrations this compound is poisonous, can kill or inhibit cell growth. Strong oxidizing agents can cause cell death in more than one way: passivity, such as necrosis due to osmotic balance disorders, and apoptosis such as active cell death due to caspation. The copper charge can cause direct cell inactivation between metal-protein interactions. Caspate enzymatic activity is regulated by oxidative modification of cysteine residues and is inhibited by disulfiram thus forming a direct link between sulfur protein and drugs. The conclusion of this study showed that the complex compound Cu (II) -2,4,5-triphenyl-1 H-imidazole showed significant properties against cancer cells. The application of complex compounds is more reactive in T74D breast cancer cells compared to HeLa cervical cancer cells. The mechanism how complex compounds emit anticancer effects is still unknown.
Author: Teguh Hari Sucipto, S.Si., M.Si.
Article: Synthesis and anti-cancer activity of copper (II) complex with 2,4,5-triphenyl-1 H -imidazole ligand
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