Bioinorganic Chemistry and Applications

(E)-N,N-Dimethyl-2-((E-1-(2-(p-tolyl)hydrazono)propan-2-ylidene)hydrazine-1-carbothioamide (DMPTHP) and their Zn(II) and Cd(II) complexes have been synthesized and characterized. Different tools of analysis such as elemental analyses, IR, mass spectra, and ¹H-NMR measurements were used to elucidate the structure of the synthesized compounds. According to these spectral results, the DMPTHP ligand behaved as a mononegatively charged tridentate anion. Modeling and docking studies were investigated and discussed. Novel Schiff base (DMPTHP) ligand protonation constants and their formation constants with Cd(II) and Zn(II) ions were measured in 50% DMSO solution at 15°C, 25°C, and 35°C at I = 0.1 mol·dm⁻³ NaNO₃. The solution speciation of different species was measured in accordance with pH. Calculation and discussion of the thermodynamic parameters were achieved. Both log K₁ and –ΔH₁, for M(II)-thiosemicarbazone complexes were found to be somewhat larger than log K₂ and –ΔH₂, demonstrating a shift in the dentate character of DMPTHP from tridentate in 1 : 1 chelates to bidentate in 1 : 2; M : L chelates and steric hindrance were generated by addition of the 2^nd molecule. The compounds prepared have significant activity as antioxidants, similar to ascorbic acid. It is hoped that the results will be beneficial to antimicrobial agent chemistry. The formed compounds acted as a potent antibacterial agent. Molecular docking studies were investigated and have proved that DMPTHP as antibacterial agents act on highly resistant strains of E. coli and also as an anticancer agent.

Three hexacoordinated octahedral nickel (II) complexes, [Ni (Trp-sal) (phen) (CH₃OH)] (1), [Ni (Trp-o-van) (phen) (CH₃OH)]•2CH₃OH (2), and [Ni (Trp-naph) (phen) (CH₃OH)] (3) (where Trp-sal = Schiff base derived from tryptophan and salicylaldehyde, Trp-o-van = Schiff base derived from tryptophan and o-vanillin, Trp-naph = Schiff base derived from tryptophan and 2-hydroxy-1-naphthaldehyde, phen = 1, 10-phenanthroline), have been synthesized and characterized as potential anticancer agents. Details of structural study of these complexes using single-crystal X-ray crystallography showed that distorted octahedral environment around nickel (II) ion has been satisfied by three nitrogen atoms and three oxygen atoms. All these complexes displayed moderate cytotoxicity toward esophageal cancer cell line Eca-109 with the IC₅₀ values of 23.95 ± 2.54 μM for 1, 18.14 ± 2.39 μM for 2, and 21.89 ± 3.19 μM for 3. Antitumor mechanism studies showed that complex 2 can increase the autophagy, reactive oxygen species (ROS) levels, and decrease the mitochondrial membrane potential remarkably in a dose-dependent manner in the Eca-109 cells. Complex 2 can cause cell cycle arrest in the G2/M phase. Additionally, complex 2 can regulate the Bcl-2 family and autophagy-related proteins.

Background. Acute myeloid leukemia (AML) persists to be a major health problem especially among children as effective chemotherapy to combat the disease is yet to be available. Boswellia dalzielii is a well-known herb that is traditionally used for treatment and management of many diseases including degenerative diseases. In this study, silver nanoparticles were synthesized from the phytochemicals of B. dalzielii stem bark aqueous extract. The silver nanoparticles were characterized by carrying out Fourier Transform Infrared (FTIR) spectroscopy, Energy Filtered Scanning Electron Microscopy (FESEM), X-ray diffraction, and Dynamic Light Scattering (DLS) analyses. Antioxidant capacity of the nanoparticles was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the antiproliferative effect of the nanoparticles on Kasumi-1 leukemia cells was investigated using PrestoBlue assay. Flow cytometry analysis was performed to observe the effect of the nanoparticles on the leukemia cell cycle progression. Results. Our findings revealed that the synthesized silver nanoparticles were formed from electrons of the plant phytochemicals which include aromatic compounds, ethers, and alkynes. FESEM analysis revealed that the sizes of the nanoparticles range from 12 nm to 101 nm; however, DLS analysis estimated a larger average size of the nanoparticles (108.3 nm) because it measured the hydrodynamic radii of the nanoparticles. The zeta potential of the nanoparticles was −16 nm, and the XRD pattern of the nanoparticles has distinct peaks at 38.02°, 42.94°, 64.45°, 77.20°, and 81.47°, which is typical of face-centered cubic (fcc) structure of silver. The Trolox Equivalence Antioxidant Capacity (TEAC) of the nanoparticles was estimated to be 300.91 μM Trolox/mg silver nanoparticles. The nanoparticles inhibited Kasumi-1 cell proliferation. The half minimal inhibitory concentrations (IC50s) that inhibited Kasumi-1 cell proliferation are 49.5 μg/ml and 13.25 μg/ml at 48 and 72 hours, respectively. The nanoparticles induced cell cycle arrest in the Kasumi-1 cells at S (5% increase) and G2/M (3% increase) phases. Conclusion. The nanoparticles synthesized from the stem bark extract of B. dalzielii inhibit the growth of Kasumi-1 leukemia cells by activating cell cycle arrest; thus, they are potential antileukemic agents.

The objective of root canal obturation is to achieve a fluid-tight seal. Recently, GuttaFlow bioseal (GB), a root canal sealer composed of polydimethylsiloxane, gutta-percha particles, and bioactive glass ceramics, has been developed, to enhance the sealing ability of root canal filling material. The objective of this study was to assess the sealing ability of GB using a subnanoliter-scaled fluid-flow measuring device and to compare with that of AH Plus (AH). The fluid flow in root canal-filled teeth using either gutta-percha cone (GP) with AH (GAR; n = 10) or GP with GB (GBR; n = 10) and in GP inserted in AH blocks (GA; n = 10) or GP inserted in GB blocks (GB; n = 10) was measured. In addition, fluid flow in sealer blocks of AH (A; n = 10) and GB (B; n = 10), which served as negative controls, was measured. Root canal-filled teeth using GP without any sealer (GR) acted as positive controls (n = 10). The leakage was obtained by calculating the volume of moved water by time (s), after stabilization of the fluid flow was achieved. Statistical analysis was performed using the Kruskal–Wallis test and Mann–Whitney U-test with Bonferroni correction. A value less than 0.00238 (0.05/21) was considered significantly different. The mean leakages (nL/s) in the groups are as follows: GAR, 0.0958 ± 0.0543; GBR, 0.0223 ± 0.0246; GA, 0.0644 ± 0.0803; GB, 0.0267 ± 0.0182; A, 0.0055 ± 0.0057; B, 0.0052 ± 0.005; and GR, 0.2892 ± 0.3018. The mean leakage in the GBR group was lower than that in the GAR group ( = 0.001), while the mean leakages in the GA and GB groups were not significantly different. GuttaFlow bioseal can be useful in single-cone obturation technique.

Two pyridine thiazole derivatives, namely, 4-(pyridin-2-yl)-2-(2-(pyridin-2-ylmethylene)hydrazinyl)thiazole (L1) and 4-(pyridin-3-yl)-2-(2-(pyridin-4-ylmethylene)hydrazinyl)thiazole (L2), were afforded by a cyclization reaction between α-haloketone and thioamide, and their Zn(II) complexes were prepared by the reaction of ligands and corresponding metal salts, respectively, and characterized by X-ray diffraction and elemental analysis. Both crystals were obtained by ether diffusion and crystallized in a monoclinic system. The in vitro antimicrobial activity of the Zn(II) complexes and ligands was screened using the microplate reader method, and in vitro antitumor activities of the complexes were evaluated by MTT, with a view to developing new improved bioactive materials with novel properties. The biological activity studies of the compounds showed that the metal complexes were more active than the free ligands, and some compounds had absolute specificity for certain bacteria or cancer cell lines.

Hemoglobin- (Hb-) based oxygen carriers (HBOC) have for several decades been explored for treatment of hemorrhage. In our previous top-up tests, HBOC with lower in vitro prooxidant reactivity (incorporating a peroxidase or serum albumin to this end) showed a measurable but small improvement of oxidative stress-related parameters. Here, such HBOCs are tested in a hemorrhage set-up; ovine hemoglobin is also tested for the first time in such a setting, based on in vitro data showing its improved performance versus bovine Hb against oxidative and nitrosative stress agents. Indeed, ovine Hb performs better than bovine Hb in terms of survival rates, arterial tension, immunology, and histology. On the other hand, unlike in the top-up models, where the nonheme peroxidase rubrerythrin as well as bovine serum albumin copolymerized with Hb were shown to improve the performance of HBOC, in the present hemorrhage models rubrerythrin fails dramatically as HBOC ingredient (with a distinct immunological reaction), whereas serum albumin appears not feasible if its source is a different species (i.e., bovine serum albumin fares distinctly worse than rat serum albumin, in HBOC transfusions in rats). An effect of the matrix in which the HBOCs are dissolved (PBS versus gelofusine versus plasma) is noted.