Structure-activity relationship and cytotoxicity of the new thiosemicarbazide derivatives and their Cu(II) complexes against prostate and melanoma cancer cells.

In this study, eighteen new ligands (B1-B18) containing a thiosemicarbazide core were synthesized and characterized in terms of physicochemical properties, molecular docking and in vitro biological activity. The structures of eleven ligands were investigated using X-Ray diffraction and Hirschfeld Surface analysis. To study the structure-activity relationship, the organic ligands contained pyridin-2-ylmethyl, pyridin-3-ylmethyl or pyridin-4-ylmethyl moieties and various substituents. Their pharmakokinetic profiles and molecular docking results suggest high potential as new drug candidates. The complexing ability of the selected organic ligands was also evaluated, yielding five new Cu(II) complexes (Cu(B1)Cl2, Cu(B4)Cl2, Cu(B10)Cl2, Cu(B17)Cl2, Cu(B18)Cl2). The obtained results suggest the formation of the polymeric structures. All organic ligands and Cu(II) complexes were tested for anticancer activity against prostate and melanoma cancer cells (PC-3, DU-145, LNCaP, A375, G-361, SK-MEL-28) and normal fibroblasts (BJ), as well as antimicrobial activity against six selected bateria strains. Among B1-B18 compounds, B3, B5, B9, B10, B12 and B14 exhibited cytotoxic activity. The studied Cu(II) complexes were in general more active, with Cu(B1)Cl2 exhibiting antincancer activity agains all three prostate cancer cells and Cu(B10)Cl2 reaching the IC50 value equal to 88 µM against G-361 melanoma cells. Several compounds also exhibited antimicrobial activity against gram-positive and gram-negative bacteria. It was found that the type of specific substituents, especially the presence of -chloro and -dichloro substituents had a greated impact on the cytotoxicity than the position of the nitrogen atom in the pyridylacetyl moiety.

Evaluation of Antidepressive-like Behaviours and Oxidative Stress Parameters in Mice Receiving Imipramine-Zinc Complex Compound.

The study aimed to evaluate the antidepressant-like effects of an imipramine-zinc (IMI-Zn) complex compound on mice and assess the level of oxidative stress parameters. The research also investigated whether the IMI-Zn complex showed superior antidepressant activity compared to individual treatments of both compounds at effective doses and their joint administration at subtherapeutic doses. The study was conducted on mice. Forced swim (FST), tail suspension (TST), and locomotor activity tests were used for behavioral studies. The results demonstrated the IMI-Zn complex's dose-dependent antidepressant potential when orally administered to mice. Its efficacy was similar to the separate administration of therapeutic doses of imipramine (IMI) and zinc (Zn) and their joint administration at subtherapeutic doses. Moreover, subjecting mice to acute stress did not significantly affect the activity of on glutathione peroxidase (GPX), glutathione reductase (GR), and total antioxidant status (TAS), possibly due to the short exposure time to the stress stimulus. By developing the IMI-Zn complex, it might be possible to simplify the treatment approach, potentially improving patient compliance by combining the therapeutic effects of both IMI and Zn within a single compound, thus addressing one of the contributing factors to non-compliance in depression therapy. The IMI-Zn complex could be a valuable strategy to optimize therapeutic outcomes and balance efficacy and tolerability.

Anticancer and antimicrobial activity of new copper (II) complexes.

In this study, three new organic ligands N'-(benzylidene)-6-chloropyrazine-2-carbohydrazonamide (L1), 6-chloro-N'-(4-nitrobenzylidene)picolinohydrazonamide(L2), and N'-(benzylidene)-4-chloropicolinohydrazonamide (L3) and three copper coordination compounds (Cu(L1)Cl2, Cu(L2)Cl2 and Cu(L3)Cl2) based on them were synthesized. All obtained compounds were characterized using appropriate analytical techniques: elemental analysis (EA), thermogravimetric analysis (TG-DTG), Fourier transform infrared spectroscopy (FTIR) and flame-atomic absorption spectrometry (F-AAS). These methods of physicochemical analyses helped to assume that the complexation in three cases proceeds in a bidentate manner. The X-ray investigation confirmed the synthesis pathway and molecular structures for L1 and L3 ligands. The antimicrobial activity of the obtained compounds was then comprehensively investigated, where Cu(L3)Cl2 showed the strongest antibacterial properties against all tested bacteria (Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli). LN229 human glioma cells and BJ human normal fibroblasts cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The effect of complexing on antitumor activity has been investigated. The ligand L1 and its complex showed similar activity against normal cells while complexation increases toxicity against cancer cells in concentrations of 50 and 100 µM. For the one pair of ligand/complex compounds the apoptosis detection, cell cycle analysis and gene expression analysis (qRT-PCR) were performed. Cu(L1)Cl2 showed the stronger toxic effect in comparison with L1 due to the population of early apoptotic cells which revealed metabolic activity in MTT assay.

In Silico ADME and Toxicity Prediction of Benzimidazole Derivatives and Its Cobalt Coordination Compounds. Synthesis, Characterization and Crystal Structure.

As a result of the synthesis, three new solids, cobalt (II) coordination compounds with benzimidazole derivatives, and chlorides were obtained. The ligands that were used in the synthesis were specially synthesized and were commercially unavailable. During the synthesis, a single crystal of the complex with the L1 ligand was obtained and the crystal structure was refined. All coordination compounds were characterized by elemental analysis, infrared spectroscopy, and thermogravimetric analysis. All the obtained data allowed one to determine the formulas of the new compounds, as well as to determine the method of metal-ligand coordination. Thermal analysis allowed to know the temperature stability of the compounds, solids intermediate and final products of pyrolysis. Additionally, volatile decomposition and fragmentation products have been identified. The toxicity of the compounds and their bioavailability were determined using in silico methods. By predicting activity on cell lines, the potential use of compounds as chemotherapeutic agents has been specified. The blood-brain barrier crossing and the gastrointestinal absorption were defined. Pharmaceutical biodistribution was also simulated.

Synthesis and Biological Evaluation of Thiazole-Based Derivatives with Potential against Breast Cancer and Antimicrobial Agents.

Investigating novel, biologically-active coordination compounds that may be useful in the design of breast anticancer, antifungal, and antimicrobial agents is still the main challenge for chemists. In order to get closer to solving this problem, three new copper coordination compounds containing thiazole-based derivatives were synthesized. The structures of the synthesized compounds and their physicochemical characterization were evaluated based on elemental analysis, 1H and l3C nuclear magnetic resonance (NMR), flame atomic absorption spectroscopy (F-AAS), single-crystal X-ray diffraction, thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR). The pharmacokinetics were studied using SwissADME. The results obtained from the computational studies supported the results obtained from the MTT analysis, and the antimicrobial activity was expressed as the minimum inhibitory concentration (MIC).

Design, Synthesis, and Characterization of Novel Coordination Compounds of Benzimidazole Derivatives with Cadmium.

Four complexes of Cd(II) with benzimidazole derivatives were synthesized and named C1, C2, C3, and C4. All coordination compounds were characterized through elemental analysis (EA), flame atomic absorption spectrometry (FAAS), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis coupled with mass spectrometry) (TG-MS), a cytotoxicity assay (MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide)), and computational chemical analysis for absorption, distribution, metabolism, and excretion (ADME). All of the obtained results are compatible and are consistent with the respective structures of the obtained compounds and their properties. The various techniques used allowed the determination of the composition, proposed structure of the compounds, their thermal stability and thermal properties, and the method of coordination between the metal (II) ion and the ligand. The ADME technique was also used to estimate the physicochemical and biological properties. The antitumor activity of the compounds was determined with an MTT assay on the glioblastoma (T98G), neuroblastoma (SK-N-AS), and lung adenocarcinoma (A549) cell lines, as well as normal human skin fibroblasts (CCD-1059Sk). Compound C2 was found to have potential antitumor properties and to be effective in inhibiting the growth of neuroblastoma cells. The antimicrobial activity of Cd complexes, free ligands, and reference drugs was tested against six strains of Gram-positive bacteria, five strains of Gram-negative rods, and three strains of yeasts. Compound C3 significantly increased activity against Gram-positive bacteria in comparison to the ligand.

New Derivatives of 5-((1-Methyl-Pyrrol-2-yl) Methyl)-4-(Naphthalen-1-yl)-1,2,4-Triazoline-3-Thione and Its Coordination Compounds with Anticancer Activity.

A new ligand 5-((1-methyl-pyrrol-2-yl) methyl)-4-(naphthalen-1-yl)-1,2,4-triazoline-3-thione (C15) and its metal complexes with formulae: Mn(C15)Cl2MeOH (1), Fe(C15)Cl2MeOH (2), Ni(C15)Cl2MeOH (3), Cu(C15)2Cl2 (4) and Zn(C15)4Cl2 (5) have been synthesized. The C15 ligand and complexes were characterized by NMR, elemental analysis, FT-IR, EPR, magnetic and TGA studies. The anticancer activities of the organic ligand (C15) and complexes (1-5) were evaluated against human colon adenocarcinoma (HT29) and human lung (A549) cancer cell lines. The complex (1) exhibited potential activity at concentration of 794.37 µM (A549) and 654.31 µM (HT29) in both cancer cells. The complex (3) showed significant activity against the HT29 cancer cell line with an IC50 value of 1064.05 µM. This article highlights some of the metals that have become important in the development of new coordination complexes and the treatment of cancer. Additionally, for C15, the toxicity was predicted by ADMET analysis and molecular docking.

New Coordination Compounds Based on a Pyrazine Derivative: Design, Characterization, and Biological Study.

New coordination compounds of Mn(II), Fe(III), Co(II), and Ni(II) and the biologically active ligand L (N'-benzylidenepyrazine-2-carbohydrazonamide) were synthesized and characterized by appropriate analytical techniques: elemental analysis (EA), thermogravimetric analysis (TG-DTG), infrared spectroscopy (FTIR), and flame-atomic absorption spectrometry (F-AAS). The biological activity of the obtained compounds was then comprehensively investigated. Rational use of these compounds as potential drugs was proven by ADME analysis. All obtained compounds were screened in vitro for antibacterial, antifungal, and anticancer activities. Some of the studied complexes exhibited significantly higher activity than the ligand alone.

Zinc Coordination Compounds with Benzimidazole Derivatives: Synthesis, Structure, Antimicrobial Activity and Potential Anticancer Application.

Developing new, smart drugs with the anticancer activity is crucial, especially for cancers, which cause the highest mortality in humans. In this paper we describe a series of coordination compounds with the element of health, zinc, and bioactive ligands, benzimidazole derivatives. By way of synthesis we have obtained four compounds named C1, C2, C4 and C4. Analytical analyses (elemental analysis (EA), flame atomic absorption spectrometry (FAAS)), spectroscopic (Fourier transform infrared spectroscopy (FT-IR), mass spectrometry (MS)) and thermogravimetric (TG) methods and the definition of crystal structures were used to explore the nature of bonding and to elucidate the chemical structures. The collected analytical data allowed the determination of the stoichiometry in coordination compounds, thermal stability, crystal structure and way of bonding. The cytotoxicity effect of the new compounds as a potential antitumor agent on the glioblastoma (T98G), neuroblastoma (SK-N-AS) and lung adenocarcinoma (A549) cell lines and human normal skin fibroblasts (CCD-1059Sk) was also determined. Cell viability was determined by the MTT assay. The results obtained confirmed that conversion of ligands into the respective metal complexes significantly improved their anticancer properties. The complexes were screened for antibacterial and antifungal activities. The ADME technique was used to determine the physicochemical and biological properties.

Antitumor Activity and Physicochemical Properties of New Thiosemicarbazide Derivative and Its Co(II), Ni(II), Cu(II), Zn(II) and Cd(II) Complexes.

A novel biologically active thiosemicarbazide derivative ligand L (N-[(phenylcarbamothioyl)amino]pyridine-3-carboxamide) and a series of its five metal(II) complexes, namely: [Co(L)Cl2], [Ni(L)Cl2(H2O)], [Cu(L)Cl2(H2O)], [Zn(L)Cl2] and [Cd(L)Cl2(H2O)] have been synthesized and thoroughly investigated. The physicochemical characterization of the newly obtained compounds has been performed using appropriate analytical techniques, such as 1H and l3C nuclear magnetic resonance (NMR), inductively coupled plasma (ICP), thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR) and magnetic measurements. In order to study the pharmacokinetic profile of the compounds, ADMET analysis was performed. The in vitro studies revealed that the synthesized compounds exhibit potent biological activity against A549 human cancer cell line.

Antitumor Activity against A549 Cancer Cells of Three Novel Complexes Supported by Coating with Silver Nanoparticles.

A novel biologically active organic ligand L (N'-benzylidenepyrazine-2-carbohydrazonamide) and its three coordination compounds have been synthesized and structurally described. Their physicochemical and biological properties have been thoroughly studied. Cu(II), Zn(II), and Cd(II) complexes have been analyzed by F-AAS spectrometry and elemental analysis. The way of metal-ligand coordination was discussed based on FTIR spectroscopy and UV-VIS-NIR spectrophotometry. The thermal behavior of investigated compounds was studied in the temperature range 25-800 °C. All compounds are stable at room temperature. The complexes decompose in several stages. Magnetic studies revealed strong antiferromagnetic interaction. Their cytotoxic activity against A549 lung cancer cells have been studied with promising results. We have also investigated the biological effect of coating studied complexes with silver nanoparticles. The morphology of the surface was studied using SEM imaging.

Influence of Incorporation of Different dn-Electron Metal Cations into Biologically Active System on Its Biological and Physicochemical Properties.

Three new compounds, namely [HL]2+[CuCl4]2-, [HL]2+[ZnCl4]2-, and [HL]2+[CdCl4]2- (where L: imipramine) were synthesized and their physicochemical and biological properties were thoroughly investigated. All three compounds form isostructural, crystalline systems, which have been studied using Single-Crystal X-ray diffraction analysis (SC-XRD) and Fourier-transform infrared spectroscopy (FTIR). The thermal stability was investigated using thermogravimetric analysis (TGA) and melting points for all compounds have been determined. Magnetic measurements were performed in order to study the magnetic properties of the compounds. The above mentioned techniques allowed us to comprehensively examine the physicochemical properties of the newly obtained compounds. The biological activity was investigated using the number of Zebrafish tests, as it is one of the most common models for studying the impact of newly synthesized compounds on the central nervous system (CNS), since this model is very similar to the human CNS.

Cytotoxic Activity against A549 Human Lung Cancer Cells and ADMET Analysis of New Pyrazole Derivatives.

Two new pyrazole derivatives, namely compound 1 and compound 2, have been synthesized, and their biological activity has been evaluated. Monocrystals of the obtained compounds were thoroughly investigated using single-crystal X-ray diffraction analysis, FTIR spectroscopy, and NMR spectroscopy. The results gathered from all three techniques are in good agreement, provide complete information about the structures of 1 and 2, and confirm their high purity. Thermal properties were studied using thermogravimetric analysis; both 1 and 2 are stable at room temperature. In order to better characterize 1 and 2, some physicochemical and biological properties have been evaluated using ADMET analysis. The cytotoxic activity of both compounds was determined using the MTT assay on the A549 cell line in comparison with etoposide. It was determined that compound 2 was effective in the inhibition of human lung adenocarcinoma cell growth and may be a promising compound for the treatment of lung cancer.

Characterization of Metal-Bound Benzimidazole Derivatives, Effects on Tumor Cells of Lung Cancer.

Four new ligands and four new copper (II) coordination compounds were prepared and characterized by chemical, elemental analysis, cytotoxicity, and FTIR spectroscopy (Fourier transform infrared spectroscopy). The nature of metal-ligand coordination was investigated. The thermal properties of complexes in the solid state were studied using TG-MS techniques (thermogravimetric analysis coupled with mass spectrometry) under dynamic flowing air atmosphere to analyze the principal volatile thermal decomposition and fragmentation products that evolved during thermolysis. The intermediate and final solid thermolysis products were also determined. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay was used to evaluate active metabolic cells as an IC50 (half maximal inhibitory concentration). The relationship between antitumor activity and the position of nitrogen atoms in the organic ligand has been shown.

Influence of Complexation of Thiosemicarbazone Derivatives with Cu (II) Ions on Their Antitumor Activity against Melanoma Cells.

A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested. The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway and assumed molecular structures of analyzed thiosemicarbazones. The conformational preferences of the thiosemicarbazone system were characterized using theoretical calculations by AM1 method. Selected compounds were converted into complexes of Cu (II) ions. The effect of complexing on anti-tumor activity has been investigated. The copper(II) complexes, with Schiff bases T1, T10, T12, T13, and T16 have been synthesized and characterized by chemical and elemental analysis, FTIR spectroscopy and TGA method. Thermal properties of coordination compounds were studied using TG-DTG techniques under dry air atmosphere. G361, A375, and SK-MEL-28 human melanoma cells and BJ human normal fibroblast cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The compounds with the most promising anti-tumour activity were then selected and their cytotoxicity was verified with cell cycle analysis and apoptosis/necrosis detection. Additionally, DNA damages in the form of a basic sites presence and the expression of oxidative stress and DNA damage response genes were evaluated. The obtained results indicate that complexation of thiosemicarbazone derivatives with Cu (II) ions improves their antitumor activity against melanoma cells. The observed cytotoxic effect is associated with DNA damage and G2/M phase of cell cycle arrest as well as disorders of the antioxidant enzymes expression.

Structural, Spectroscopic, Thermal, and Magnetic Properties of a New Dinuclear Copper Coordination Compound with Tiglic Acid.

The first coordination compound of copper and tiglic acid named tetrakis(µ-tiglato)bis(tiglic acid)dicopper(II) was synthesized and crystallized from water solution. Its structure was determined and analyzed based on X-ray diffraction measurement. The paddle-wheel coordination system of the investigated compound was compared with other similar copper structures known in the literature. The Hirshfeld analysis was used for the detailed analysis of intermolecular interaction. The new compound was also characterized in terms of infrared absorption, thermal, and magnetic properties. The antiferromagnetic coupling of copper ions was found.

Natural Rubber Biocomposites Filled with Phyto-Ashes Rich in Biogenic Silica Obtained from Wheat Straw and Field Horsetail.

The rich structural hierarchy of plants permits the obtainment of porous structures which can be expected to show improved performances in fields such as pharmaceuticals and cosmetics, catalysis, drug delivery, adsorption, separation or sensors in various chemical reactions. On the other hand, porous materials can be an active additive to polymer composites. The aim of the study was to obtain natural rubber (NR) biocomposites with the addition of phyto-ashes reach in biogenic silica from plant biomass. For the production of bioadditives, a two-stage method of high-temperature heat treatment was used, preceded by acid hydrolysis of plant tissues in the form of horsetail and wheat straw. Hydrolysis was performed with hydrochloric and citric acid. The efficiency of the processes and their influence on the elemental composition, surface morphology, thermal stability and particle size of the fillers were determined. Modified bioadditives were introduced into the elastomer matrix and their processing properties, as well as the vulcanization characteristics, were examined. Static mechanical properties (tensile strength, elongation at break, stress at 100%, 200% and 300% elongation), dynamic-mechanical analysis and the influence of additives on the cross-link density of the composites were determined. Structural analysis was performed using scanning electron microscopy. It was found that the field horsetail and cereal straw are plants rich in many valuable chemical compounds, especially silica. The specific and appropriate treatment of these plants can lead to bioadditives that significantly affect the properties of rubber materials.

Synthesis, Spectroscopic, Thermal, and Catalytic Properties of Eight New Complexes of Metal(II) Formates or Propionates with Imidazole; Relationship between the Carbon Chain Length and Catalytic Activity.

In one of our previously published articles, we reported the synthesis, spectroscopic, thermal, and catalytic properties of four new M(II) acetate (where M = Co, Ni, Cu, Zn) complexes with imidazole. Presented compounds exhibited activity in the reaction on catalytic oxidation of styrene. In this study we have synthesized and investigated properties of analogous compounds, however using formates or propionates of mentioned metal cations instead of acetates. Such an approach allowed us to draw valuable conclusions concerning the relationship between the carbon chain length and catalytic activity, which is an important factor for catalyst modeling. Synthesized compounds have been thoroughly investigated using appropriate analytic techniques: AAS (Atomic Absorption Spectrometry), FTIR (Fourier-Transform Infrared Spectroscopy), and TGA (Thermogravimetric Analysis). Catalytic properties have been studied under the same previous conditions, using GC-FID (GC-chromatograph equipped with FID detector).

Investigation and Possibilities of Reuse of Carbon Dioxide Absorbent Used in Anesthesiology.

Absorbents used in closed and semi-closed circuit environments play a key role in preventing carbon dioxide poisoning. Here we present an analysis of one of the most common carbon dioxide absorbents-soda lime. In the first step, we analyzed the composition of fresh and used samples. For this purpose, volumetric and photometric analyses were introduced. Thermal properties and decomposition patterns were also studied using thermogravimetric and X-ray powder diffraction (PXRD) analyses. We also investigated the kinetics of carbon dioxide absorption under conditions imitating a closed-circuit environment.

Anti-Oxidative Activity of Alcohol-Water Extracts from Field Horsetail (Equisteum arvense) in Elastomer Vulcanizates Subjected to Accelerated Aging Processes.

The article aimed to highlight the antioxidant potential of natural extracts obtained from Equisteum arvense in elastomer vulcanizatec made of natural rubber. Horsetail extracts were prepared using four solvent systems at different volume ratios: methanol-water (50/50 and 70/30) and ethanol-water (50/50 and 70/30), which were then lyophilized and added to the polymer matrix. A deep characterization of the obtained bio-additives was performed. The obtained vulcanizates were subjected to various aging processes: thermo-oxidative, ultraviolet and solar. Then, the resistance and susceptibility of vulcanizates to selected processes of accelerated, simulated degradation were determined based on the changes in the spatial structure (network nodes), material strength and physical properties (color). The research showed the presence of polyphenols in the extracts of horsetail, which resulted in their high anti-oxidative activity. Moreover, the extracts were able to absorb UV radiation. As a consequence, they were active additives that protected rubber vulcanizates against the damaging effects of the aging processes, securing their functional properties. Samples containing natural extracts were characterized by better stability of: mechanical strength parameters, the increase in cross-linking density and color changes after simulating aging processes in comparison with the control sample.