Ruthenium (II) Complexes Based on Phenanthroline-Tetrazole as Possible Anticancer Agents.

Background: The development of platinum-based metal complexes in oncology is limited due to vigorous toxicity and drug resistance. Objectives: This work aimed to study the cytotoxic activity and apoptosis induction of ruthenium complexes in a B16F10 cell line therapy. Methods: We prepared a series of innovative Ru(II) complexes [Ru(Tzphen)(bpy)(dcbpy)]+2 (S1), [Ru(dcbpy)2(Tzphen)]+2 (S2), [Ru(Phen)2(Tzphen)]+2 (S3), [Ru(Tzphen)(bpy)2]+2 (S4), [Ru(dmbpy)2(Tzphen)]+2 (S5) based on 1,10-phenanthroline ligand containing tetrazole and their anticancer properties investigated by cytotoxicity in vitro, reactive oxygen species, apoptosis with annexin V/PI staining method, autophagy, and cell uptake. Results: S1, S2, S3, S4, and S5 complexes showed comparable cytotoxicity activity relative to cisplatin against the B16F10 model. Moreover, intracellular ROS levels increased due to the presence of the complexes. Among the investigated complexes, the cells treated with the S5 complex indicated the highest apoptotic percentage (Q3) of 14.9% compared to the controls. The cell adsorption of the complexes also showed that the S4 and S5 complexes had higher cell adsorption, better internalization, and higher fluorescence light intensity. Conclusions: The present work provides important guidance for designing and using Ru complexes in cancer therapy.

Effect of lipophilicity of amylamine and amylglycine ligands on biological activity of new anticancer cisplatin analog.

Investigation of side effects and solubility of anticancer drugs is a major challenge in chemotherapy science. Thus, design and synthesis of cisplatin analogs with higher lipophilicity as novel water-soluble anticancer drugs is valuable. In this work, two new Pt(II) complexes were synthesized with formula cis-[Pt(NH3)2(amylgly)]NO3 and cis-[Pt(amylamine)2(amylgly)]NO3, where gly is penthyl glycine as an amino acid. The new compounds were synthesized and extensively characterized using analytical techniques; spectroscopic methods, and conductivity measurement. The anticancer activity of synthesized complexes was investigated against colon cancer cell line HCT116 using MTT assay and results showed excellent anticancer activity with Cc50 values of 36 and 270 M after 24-h incubation time for cis-[Pt(NH3)2(amylgly)]NO3 and cis-[Pt(NH2-amyl)2(amylgly)]NO3, respectively; which is lower than that for cisplatin. These complexes were also interacted with highly polymerized calf thymus DNA and the binding mode of the complexes to CT-DNA was evaluated by fluorescence, circular dichroism, and UV spectroscopy. The calculation of binding and thermodynamic of Pt(II) complexes with CT-DNA can provide deeper insight into mechanism of the action of these types of complexes with nucleic acids. So, thermodynamic parameters were also determined according to isothermal titration. In comparison with cis-[Pt(NH3)2(amylgly)]NO3 in DNA interaction, the result show that cis-[Pt(NH2-amyl)2(amylgly)]NO3 has higher affinity with binding constant Kf = 8.72 mM to CT-DNA. The results indicate that cis-[Pt(amylamine)2(amylgly)]NO3 with large and bulky aliphatic group bind to CT-DNA by different modes and covalent and groove bindings were preferred mode of interaction with DNA.

catena-Poly[di-µ3-bromido-hexa-µ2-bromido-dibromidobis(O-methyl pyridine-2-carboximidate-κ(2) N,N')penta-mercury(II)].

The title compound, [Hg5Br10(C7H8N2O)2] n , contains two µ3-bridging Br atoms, six µ2-bridging Br atoms and two terminal Br atoms. One Hg(II) atom, lying on an inversion center, adopts a distorted octa-hedral geometry defined by six Br atoms. Two Hg(II) atoms adopt a distorted square-pyramidal geometry by five Br atoms and the other two Hg(II) atoms have a distorted tetra-hedral geometry by two N atoms from a chelating O-methyl pyridine-2-carboximidate ligand and two Br atoms. The Br atoms link the Hg(II) atoms into a ribbon structure along [100].

Dichloridobis(4-methyl-3,5-diphenyl-1H-pyrazole-κN)copper(II).

The asymmetric unit of the title compound, [CuCl(2)(C(16)H(14)N(2))(2)], comprises half of the complex. The Cu(II) atom lies on a crystallographic twofold rotation axis and shows a significantly distorted tetra-hedral coordination geometry. The dihedral angle between the phenyl rings is 74.3 (2)°. The crystal structure is stabilized by inter-molecular π-π inter-actions [centroid-centroid distances = 3.635 (2)-3.803 (3) Å].

Bis[bis-(3,5-dimethyl-1H-pyrazol-1-yl)-borato]cobalt(II).

The asymmetric unit of the title compound, [Co(C(10)H(16)BN(4))(2)], comprises one unit of the complex. The geometry around the Co(II) ion is a distorted tetra-hedron. The dihedral angles between the pyrazole rings in the two ligands are 47.19 (15) and 47.20 (16)°, while that between the coordination planes is 79.77 (7)°.

Bis(4-methyl-3,5-diphenyl-1H-pyrazole-κN)silver(I) nitrate.

In the title complex, [Ag(C(16)H(14)N(2))(2)]NO(3), the geometry around the Ag(I) ion is T-shaped with two short Ag-N bonds to the pyrazole ligand and one long Ag-O bond to the nitrate anion. The crystal structure is stabilized by inter-molecular N-H⋯O, C-H⋯O and C-H⋯π inter-actions.

Chlorido(1H-imidazole-κN)bis-(triphenyl-phosphane-κP)copper(I).

In the title complex, [CuCl(C(3)H(4)N(2))(C(18)H(15)P)(2)], the coordination geometry around Cu(I) is distorted tetra-hedral formed by two triphenyl-phosphane ligands, an imidazole ligand and a chloride group. An intra-molecular C-H⋯Cl inter-action occurs. The crystal packing is stabilized by inter-molecular N-H⋯Cl hydrogen bonds, which form an extended chain parallel to [010].

trans-Bis(thio-cyanato-κN)tetra-kis-(3,4,5-trimethyl-1H-pyrazole-κN)nickel(II)-3,4,5-trimethyl-1H-pyrazole (1/1).

In the title compound, [Ni(NCS)(2)(C(6)H(10)N(2))(4)]·C(6)H(10)N(2), the asymmetric unit comprises a Ni(II) complex and a co-crystallised mol-ecule of 3,4,5-trimethyl-1H-pyrazole (PzMe(3)). The Ni(II) atom is coordinated by four PzMe(3) mol-ecules and two thio-cyanate anions to define a trans N(4)S(2) distorted octa-hedral geometry. A number of intra-molecular N-H⋯N, N-H⋯S and C-H⋯N inter-actions contribute to the stability of the complex. The crystal structure is stabilized by inter-molecular N-H⋯S inter-actions, which link neighbouring mol-ecules into chains along the a axis.

(5-Hy-droxy-3-methyl-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanone monohydrate.

In the title compound, C(16)H(15)N(3)O(2)·H(2)O, the mean plane of the approximately planar pyrazole ring [maximum deviation = 0.0474 (18) Å] makes dihedral angles of 86.32 (11) and 45.04 (10)° with the phenyl and pyridine rings, respectively. The dihedral angle between the phenyl and pyridine rings is 69.62 (11)°. In the crystal, inter-molecular O-H⋯O and O-H⋯N hydrogen bonds connect the components into chains along [010]. The crystal structure is further stabilized by π-π stacking inter-actions with centroid-centroid distances of 3.7730 (12) Å.

Dibromidotetra-kis(1H-indazole-κN)copper(II).

The Cu atom in the title compound, [CuBr(2)(C(7)H(6)N(2))(4)], is surrounded by four N-heterocycles that define an N(4) square-planar geometry. The coordination geometry is distorted towards an elongated octa-hedron owing to the presence of the two Br(-) anions, which are located at about 3 Šabove and below the square plane. There are two independent molecules in the asymmetric unit, each with their Cu atom lying on an inversion centre.

1-Phenyl-2-trifluoro-methyl-4-quinolone.

In the title mol-ecule, C(16)H(10)F(3)NO, the N-bound phenyl ring is oriented nearly orthogonal to the quinolinyl ring in order to avoid steric clashes with the trifluoro-methyl substituent [dihedral angle 89.7 (1)°].