Gordana P. Radić

Synthesis, characterization and cytotoxicity of a new palladium(II) complex with a coumarine-derived ligand

The new coumarine derivative, 3-(1-(2-hydroxyethylamino)ethylidene)chroman-2,4--dione, and corresponding palladium(II) complex have been synthesized and characterized by microanalysis, infrared, (1)H and (13)C NMR spectroscopy. The proposed structure of the complex was confirmed on the basis of the X-ray structural study. The palladium(II) complex decreased viability of L929 mouse fibrosarcoma, U251 human glioma and B16 mouse melanoma cell lines in a dose dependent manner, while its ligand exhibited no significant cytotoxicity. The cytotoxic effect of the complex was comparable to that of cisplatin, and mediated by apoptosis associated with oxidative stress, mitochondrial depolarization and caspase activation. Therefore, our results indicate that newly synthesized palladium(II) complex might be a potential candidate for anticancer therapy.

Synthesis and Characterization of Zinc(II)-Complexes with S-Alkyl Derivatives of Thiosalicylic Acid

Abstract New zinc(II)-complexes with S-alkyl derivatives of thiosalicylic acid (alkyl = benzyl-(L1), methyl-(L2), ethyl-(L3), propyl-(L4), butyl-(L5)) have been synthesized and characterized by elemental microanalysis, IR spectroscopy, and 1H and 13C NMR spectroscopy. The S-alkyl derivatives of thiosalicylic acid were prepared by alkylation of thiosalicylic acid by adding alkyl halides to an alkaline water-ethanol solution, while the corresponding zinc(II)-complexes were obtained via the direct reaction of ZnCl2 with S-alkyl derivatives of thiosalicylic acid in water. Based on the microanalysis results and the IR and NMR spectra of the S-alkyl derivatives of thiosalicylic acid and the corresponding zinc(II)-complexes, we concluded that the ligands are bidentately coordinated to the zinc(II)-ion.

Stereospecific ligands and their complexes. XXIV. Synthesis, characterization and some biological properties of Pd(II) and Pt(II) complexes with R2-S,S-eddtyr

Four new platinum(II) complexes of general formula [PtCl2(R2-S,S-eddtyr)] (R = ethyl, n-propyl, n-butyl and n-pentyl); S,S-eddtyr = ethylenediamine-N,N′-di-(2,2′-di(4-hydroxy)-benzyl-acetic acid) have been synthesized and characterized by microanalysis, and infrared, 1H NMR and 13C NMR spectroscopy. The in vitro antimicrobial activity of ligands L1–L4 [L = R2-S,S-eddtyr; R = ethyl (L1), n-propyl (L2), n-butyl (L3), n-pentyl (L4)], platinum(II) complexes C1–C4 [PtCl2(R2-S,S-eddtyr)] [R = ethyl (C1), n-propyl (C2), n-butyl (C3), n-pentyl (C4)] and palladium(II) complexes C5–C8 [PdCl2(R2-S,S-eddtyr)] [R = ethyl (C5), n-propyl (C6) or n-butyl (C7) or n-pentyl (C8)] was investigated. The cytotoxicity of ligands and platinum(II) complexes was investigated using MTT assay. The interaction of platinum and palladium complexes [MCl2(R2-S,S-eddtyr)] (M = Pt or Pd) with calf thymus DNA (CT-DNA) was investigated using UV-Vis absorption and fluorescence spectroscopy. The association constant (Kb) estimated from the absorption spectral study and the quenching constant (KSV) calculated from relevant fluorescence quenching data indicate a non-covalent interaction between the metal complex and DNA. Ethidium bromide (EB) competitive studies revealed that complexes C1–C8 could interact with CT-DNA through intercalation. Furthermore, the interactions between human serum albumin (HSA) and the platinum(II) and palladium(II) complexes were also investigated by UV-Vis absorption and fluorescence spectroscopy, showing that the new complexes could strongly bind with HSA.

Synthesis and Characterization of Platinum (IV) complexes with S-alkyl Derivatives of Thiosalicylic Acid and the Crystal Structure of the S-butyl Derivative of Thiosalicylic Acid

Abstract New platinum(IV)-complexes with S-alkyl derivatives of thiosalicylic acid (alkyl = benzyl-(L1), methyl-(L2), ethyl-(L3), propyl-(L4), butyl-(L5)) have been synthesized and characterized by microanalysis, infrared spectroscopy, and 1H and 13C NMR spectroscopy. Th e bidentate S,O ligand precursor, the S-butyl derivative of thiosalicylic acid (S-bu-thiosal), was prepared, and its crystal structure was determined. Single crystals suitable for X-ray measurements were obtained by slow crystallization from a DMSO-water system. S-bu-thiosal crystallized in a P21/c space group of a monoclinic crystal system with a = 8.0732 (3) Å, b = 19.6769 (4) Å, c = 8.2291 (3) Å and Z = 4. S-bu-thiosal also has a coplanar geometry.

From Synthesis to Antibacterial Activity of Some New Palladium(II) and Platinum(IV) Complexes

Simultaneously with the rapid development of a wide range of antibacterial agents since the 1940s, bacteria have proved extremely adept at developing resistance to each new employed agent. The rapidly increasing incidence of bacterial resistance to antimicrobial agents has become a serious problem worldwide. Resistance mechanisms have been identified and described for all known antibiotics currently available for clinical use (Fluit et al., 2000).

Synthesis, characterization and biological activity of copper(II) complexes with ligands derived from β-amino acids

Two copper(II) complexes with ligands derived from β-amino acids, 2-(1-aminocyclohexyl)acetic acid L1 and 2-(1-amino-4-(tert-butyl)cyclohexyl)acetic acid L2, were synthesized and characterized by microanalysis, infrared, UV–Vis and EPR spectra. The spectroscopically predicted structure of the square-planar copper(II) complex with 2-(1-aminocyclohexyl)-acetic acid C1 was confirmed by single-crystal X-ray analysis. The biological activities (antitumor activities and interaction with DNA) of the compounds were also investigated. The interactions of both complexes with calf thymus (CT) and herring testes (HT) DNA were examined by stopped-flow spectroscopy, by absorption (UV–Vis) and by emission spectral studies (ethidium bromide displacement studies). Both complexes were found to react a bit faster with HT-DNA than with CT-DNA. The obtained binding constants suggested a moderate intercalative binding mode between the complexes and DNA. In addition, fluorescence spectrometry of bovine serum albumin with the complexes showed a good fluorescence quenching of the complexes. The obtained copper(II) complexes have a relatively low cytotoxic effect on murine mammary carcinoma cell line, 4T1, a moderate effect on murine colon carcinoma cell line, CT26, and a relatively high cytotoxicity toward murine lung cancer cells, LLC1.

DNA binding and antitumor activities of platinum(IV) and zinc(II) complexes with some S-alkyl derivatives of thiosalicylic acid

A series of complexes of platinum(IV) (C1–C5) and zinc(II) (C6–C10) with S-alkyl derivatives of thiosalicylic acid were prepared and characterized. The interactions of the complexes with calf thymus DNA were analyzed by absorption (UV–Vis) and emission spectral studies (ethidium bromide displacement studies). The cytotoxic activities of complexes C1–C10 were determined against mouse B cell lymphocytic leukemia cells (BCL1), human B-prolymphocytic leukemia (JVM-13), mouse mammary carcinoma cells (4T1), and human mammary carcinoma cells (MDA-MB-468) and compared to the activities of the free ligand precursors and cisplatin. The cytotoxicities of the platinum(IV) and zinc(II) complexes toward mouse tumor cell lines were higher compared with their effects on human tumor cell lines. The zinc(II) complex C9 showed the highest antitumor activity toward the tested human cell lines, while the platinum(IV) complex C4 exhibited the highest antitumor activity toward mouse BCL1 and 4T1 cells. Both C4 and C9 have ligands derived from S-propyl thiosalicylic acid.

Synthesis, Characterization, and Cytotoxicity of Binuclear Cooper(II)-Complexes with some S-Alkenyl Derivatives of Thiosalicyclic Acid

Abstract New complexes of copper(II) with S-alkenyl derivatives of thiosalicylic acid (alkenyl = propenyl-(L1), isobutenyl-(L2)) have been synthesized and characterized by microanalysis, infrared spectra, magnetic measurements, and by NMR spectra. The cytotoxic activity of two newly synthesized precursor S-alkenyl derivatives of thiosalicylic acid were tested using an MTT colorimetric technique on HCT-116 human colon carcinoma cells. The cytotoxic effect of the copper(II)- complexes were higher compared to the cytotoxicity of the corresponding ligand (for concentrations from 31.25 to 250 μM). Copper(II)-complexes showed a slightly lower cytotoxicity compared to cisplatin. Complexes of copper(II) with S-alkenyl derivatives of thiosalicylic acid (at concentrations from 250 to 1000 μM) had a cytotoxic effect on HCT-116 cells compared to cisplatin.

Antibacterial and antibiofilm screening of new platinum(IV) complexes with some s-alkyl derivatives of thiosalicylic acid

The influence of 5 new Platinum(IV) (Pt(IV)) complexes with S-alkyl derivatives of thiosalicylic acid (C1-benzyl, C2-methyl, C3-ethyl, C4-propyl and C5- butyl) was studied on 16 strains of bacteria. Antibacterial activity was tested using microdilution method with resazurin while antibiofilm activity was observed by tissue culture plate method, using doxycycline as a positive control. The results were expressed as minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and biofilm inhibitory concentration (BIC). The best result on Gram positive bacteria exhibited C1 and MIC was <7.81μg/ml against Staphylococcus aureus ATCC 25923. Bifidobacterium animalis subsp. lactis (probiotic) was sensitive to C2 (MIC at 15.625 μg/ml). The highest sensitivity of Gram negative bacteria was observed in Escherichia coli ATCC 25922 treated with C1, C2, C3 and C4, in Proteus mirabilis ATCC 12453 treated with C1, and in Pseudomonas aeruginosa treated with C2, C3 and C5 (all MICs at 250 μg/ml). The C2 complex were more efficient as antibiofilm agents and the best results were obtained with C2 acting against S. aureus and S. aureus ATCC 25923 biofilms. In conclusion, we noticed that the tested compounds exhibited promising properties as antibacterial and antibiofilm agents.

Benzyl 2-(benzylsulfanyl)benzoate.

In the title compound, C21H18O2S, the central aromatic ring makes dihedral angles of 5.86 (12) and 72.02 (6)° with the rings of the terminal O-benzyl and S-benzyl groups, respectively. The dihedral angle between the peripheral phenyl rings is 66.16 (6)°. In the crystal, molecules are linked by pairs of C—H⋯O hydrogen bonds, forming inversion dimers. These dimers are linked via C—H⋯π interactions, forming a three-dimensional network.