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A set of dinuclear copper(I) complexes with the general formula [Cu2(μ-dppm)2(N^N)2]2+ were synthesized and characterized by 1HNMR, 31PNMR, and elemental analysis. The high-resolution mass spectra clearly illustrated isotopic pattern for the proposed dinuclear systems. The binding of the complexes toward human serum albumin (HSA) were evaluated, highlighting good binding affinities influenced by the nature of the substituted-diimine. The complexes induce changes in both the α-helix and the microenvironment structures of HSA. The HSA-bindings were modelled by molecular docking; [Cu2(μ-dppm)2(dppz)2][ClO4]2 (3) displays the highest binding score toward HSA due to the ability of dppz in establishing π-interactions. The anticancer properties of 1, 2 and 3 were screened against COLO 205, RCC-PR, HepGII and LLC-MK2 cell lines and the results were discussed. Complex 3 has better IC50 against all the cancer cell lines than that observed for cisplatin, but still lower than the cytotoxicity of Sunitinib. Moreover, complex 3 has higher selectivity towards cancer cells over normal cells when compared to cisplatin and sunitinib. [ABSTRACT FROM AUTHOR]

CuBr(PPh3)2(4,6-dimethylpyrimidine-2-thione) (Cu-L) was synthesized by stirring CuBr(PPh3)3 and 4,6-dimethylpyrimidine-2-thione in dichloromethane. The crystal structure of Cu-L was obtained, and indicated that the complex adopts a distorted tetrahedral structure with several intramolecular hydrogen bonds. Moreover, a centrosymmetric dimer is formed by the intermolecular hydrogen bonding of the bromine acceptor created by symmetry operation 1−x, 1−y, 1−z to the methyl group (D3 = C42) of the pyrimidine–thione ligand. HSA-binding of Cu-L and its ligand were evaluated, revealing that Cu-L binds to HSA differently than its ligand. The HSA-bindings were modeled by molecular docking, which suggested that Cu-L binds to the II A domain while L binds between the I B and II A domains. Anticancer activities toward OVCAR-3 and HeLa cell lines were tested and indicated the significance of the copper center in enhancing the cytotoxic effect; negligible toxicities for L and Cu-L were observed towards a non-cancer cell line. The current study highlights the potential of copper(I)-phosphine complexes containing thione ligands as therapeutic agents. [ABSTRACT FROM AUTHOR]

A set of copper(I) coordination compounds with general formula [CuBr(PPh3)(dppz-R)] (dppz-R = dipyrido[3,2-a:2',3'-c]phenazine (Cu-1), 11-nitrodipyrido[3,2-a:2',3'-c]phenazine (Cu-2), 11-cyanodipyrido[3,2-a:2',3'-c]phenazine (Cu-3), dipyrido[3,2-a:2',3'-c]phenazine-11-phenone (Cu-4), 11,12-dimethyldipyrido[3,2-a:2',3'-c]phenazine (Cu-5)) have been prepared and characterized by elemental analysis, 1H-NMR and 31P-NMR spectroscopies as well as mass spectrometry. The structure of Cu-1 was confirmed by X-ray crystallography. The effect of incorporating different functional groups on the dppz ligand on the binding into CT-DNA was evaluated by absorption spectroscopy, fluorescence quenching of EtBr-DNA adducts, and viscosity measurements. The functional groups affected the binding modes and hence the strength of binding affinities, as suggested by the changes in the relative viscosity. The differences in the quenching constants (Ksv) obtained from the fluorescence quenching assay highlight the importance of the functional groups in altering the binding sites on the DNA. The molecular docking data support the DNA-binding studies, with the sites and mode of interactions against B-DNA changing with the different functional groups. Evaluation of the anticancer activities of the five copper compounds against two different cancer cell lines (M-14 and MCF-7) indicated the importance of the functional groups on the dppz ligand on the anticancer activities. Among the five copper complexes, the cyano-containing complex (Cu-3) has the best anticancer activities. [ABSTRACT FROM AUTHOR]

A set of five gold complexes with the general formula Au(PR3)(C≡C-C6H4-4-R′) (R = PPh3, R′ = –CHO (1), R = PCy3, R′ = –CHO (2), R = PPh3, R′ = –N=CH-C6H4-2-OH (3), R = PPh3, R′ = –N=CH-C6H4-4-OH (4), R = PCy3, R′ = –N=CH-C6H4-2-OH (5)) were synthesized and characterized by elemental analysis, 1H-NMR spectroscopy, 31P-NMR spectroscopy, and mass spectrometry. The structures of complexes 2 and 5 were determined by X-ray crystallography. The effects of the structural modifications on the protein binding affinities and anticancer activities of the five gold complexes were assessed. Fluorescence quenching experiments to assess binding to human serum albumin (HSA) revealed that the Schiff base complexes (3, 4, and 5) had binding constants that were superior to their parent aldehyde complexes and highlighted the position of the hydroxy group because complex 4 (4-hydroxy) had a binding constant 6400 times higher than complex 3 (2-hydroxy). The anticancer activities of the complexes against the OVCAR-3 (ovarian carcinoma) and HOP-62 (non-small-cell lung) cancer cell lines showed that the Schiff bases (3–5) were more cytotoxic than the aldehyde-containing complexes (1 and 2). Notably, compound 4 had cytotoxic activity comparable to that of cisplatin against OVCAR-3, demonstrating the significance of the para position for the hydroxy group. Molecular docking studies against the enzyme thioredoxin reductase (TrxR) and human serum albumin were conducted, with docking scores in good agreement with the experimental data. The current study highlights how small structural modifications can alter physiochemical and anticancer properties. Moreover, this simple design strategy using the aldehyde group can generate extensive opportunities to explore new gold(I)-based anticancer drugs via condensation, cyclization, or nucleophilic addition reactions of the aldehyde. [ABSTRACT FROM AUTHOR]

A set of dinuclear copper(I) complexes with the general formula [Cu2(μ-dppm)2(N^N)2]2+ were synthesized and characterized by 1HNMR, 31PNMR, and elemental analysis. The high-resolution mass spectra clearly illustrated isotopic pattern for the proposed dinuclear systems. The binding of the complexes toward human serum albumin (HSA) were evaluated, highlighting good binding affinities influenced by the nature of the substituted-diimine. The complexes induce changes in both the α-helix and the microenvironment structures of HSA. The HSA-bindings were modelled by molecular docking; [Cu2(μ-dppm)2(dppz)2][ClO4]2 (3) displays the highest binding score toward HSA due to the ability of dppz in establishing π-interactions. The anticancer properties of 1, 2 and 3 were screened against COLO 205, RCC-PR, HepGII and LLC-MK2 cell lines and the results were discussed. Complex 3 has better IC50 against all the cancer cell lines than that observed for cisplatin, but still lower than the cytotoxicity of Sunitinib. Moreover, complex 3 has higher selectivity towards cancer cells over normal cells when compared to cisplatin and sunitinib. [ABSTRACT FROM AUTHOR]

• A Gold(I)-Antipyrine conjugate compound was synthesized. • Introducing antipyrine moiety in Au(I)-Alkynyls altered the biomolecule-binding. • The gold(I)-antipyrine exhibits good cytotoxic effects against two cancer cell lines. • Cell cycle analysis for Au-Antipyrine complex indicated late apoptotic pathway. A Gold(I)-antipyrine conjugate compound {Au(PPh 3)(C CC 6 H 4 –4-CH N-antipyrine) (4) was synthesized and the new complex was characterized by different spectroscopic techniques. DNA-binding and BSA-binding were performed for the Au-antipyrine compound (4), showing that the synthesized complex exhibits better binding affinities against BSA compared to Au(PPh 3)(C CPh) (5) while both have comparable DNA-binding. The gold(I)-antipyrine compound was tested against HepG2 and MCF-7 human cancer cell lines, exhibiting better cytotoxic effects compared to its ligand but comparable to that of Au(PPh 3)(C CPh) (5). Despite the comparable anticancer properties of both 4 and 5 described herein, the presence of the antipyrine moiety altered the biomolecule-binding of gold(I) alkynyl complexes. Compared to cisplatin, the gold(I) complexes possess slightly less anticancer properties against both cell lines. Flow cytometry analysis was performed for Au-antipyrine complex, indicating apoptotic cell death pathway (late apoptosis) but via different mechanisms from that of cisplatin (early apoptosis) as can be seen from the differences in the cell cycle analysis at different cell phases. [Display omitted] [ABSTRACT FROM AUTHOR]