Abstract
The syntheses of [Cu(PPh3)2(L)]NO3 and [Cu(PPh3)2(L-SO3Na)]NO3 were achieved through the reaction of Cu(PPh3)2NO3 and equimolar amount of the ligands (L = 5,6-diphenyl-3-[2-pyridyl]-1,2,4-triazine; LSO3Na = 5,6-diphenyl-3-[2-pyridyl]-1,2,4-triazine-4,4′-disulfonic acid disodium salt). The complexes were characterized by NMR and IR spectroscopy and mass spectrometry. The compounds exhibit similar absorption and emission spectra, suggesting a similar electronic structure. Ct-DNA binding studies show the strong influence of the net charge as Cu-L (positively charged) is able to bind to ct-DNA while Cu-LSO3Na (negatively charged) is not. The net charge of the complexes affects the thermodynamic and kinetic binding parameters toward human serum albumin. HSA-binding of the complexes was further investigated by molecular docking, revealing different binding sites on the HSA protein as a function of the net charge. The different anticancer activities of the complexes towards ovcar-3 and hope-62 cancer cell lines are suggestive of a role for the overall charge of the complexes. Interaction with the DNA is not the major mechanism for this class of complexes. The overall net charge of the pharmacophore (anticancer agent) should be a key consideration in the design of anticancer metal complexes.
Highlights
Several transition-metal complexes, mainly containing platinum, have been approved or are currently in clinical trials for chemotherapy
Two complexes were synthesized with the formula [Cu(PPh3)2(L)]NO3 and [Cu(PPh3)2(L-SO3Na)]NO3, and the DNA-binding, protein-binding and anticancer activities were evaluated to assess the role of the complex net charge
For 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine, the reaction was performed in dichloromethane
Summary
Several transition-metal complexes, mainly containing platinum, have been approved or are currently in clinical trials for chemotherapy. A set of copper(I) complexes of the type [CuX(N^N)(tris-(2-cyanoethyl)phosphine)] has been synthesized and evaluated for their in vitro antineoplastic properties against several cancer cell lines, highlighting that the most effective complex was the one with a dipyrido-[3,2-d:2′,3′-f]-quinoxaline ligand [11]. A set of complexes with the general formula [CuBr(PPh3)(N^N)] was examined for their anticancer activities, the authors concluding that complexes with 3-[2-pyridyl]-5,6-diphenyl-1,2,4-triazine and dipyrido[3,2a:2′,3′-c]phenazine (dppz) exhibited better cytotoxicity against several cancer cell lines than complexes with substituted phenanthroline and bipyridines [12]. Copper(I) complexes including diimine ligands with water-solubilizing groups have been examined for their in vitro anticancer potential against human tumor cell lines, exhibiting moderate to high cytotoxic activities and with potential to overcome cisplatin resistant cell lines [17]. Two complexes were synthesized with the formula [Cu(PPh3)2(L)]NO3 and [Cu(PPh3)2(L-SO3Na)]NO3, and the DNA-binding, protein-binding and anticancer activities were evaluated to assess the role of the complex net charge
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