Therapeutic potential of coumarin bearing metal complexes: Where are we headed?

The successfully application of some metallodrugs such as salvarsan, silver sulfadiazine and cisplatin in modern medicine launched the biological investigation of organometallic and metal-organic complexes. The availability and tunability of various ligands including N-heterocycles, phosphines, N-heterocyclic carbenes present an extended research area to chemists. In recent years, the preparation of the metal complexes of bioactive organic compounds is a new strategy. Coumarin derivatives are one of the classes of compounds used for this purpose, and many complexes of coumarin derivatives were prepared for enhanced biological activity, especially anticancer and antimicrobial. In this paper, we discuss the current situation of this topic.

Water Soluble Coumarin Quaternary Ammonium Chlorides: Synthesis and Biological Evaluation.

In the present study, coumarin-bearing three pyridinium and three tetra-alkyl ammonium salts were synthesized. The compounds were fully characterized by 1 H- and 13 C-NMR, LC/MS and IR spectroscopic methods and elemental analyses. The cytotoxic properties of all compounds were tested against human liver cancer (HepG2), human colorectal cancer (Caco-2) and non-cancer mouse fibroblast (L-929) cell lines. Some compounds performed comparable cytotoxicity with standard drug cisplatin. Antibacterial properties of the compounds were tested against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis bacteria, but the compounds did not have any antibacterial effect against both bacteria. Enzyme inhibitory properties of all compounds were tested on the activities of human carbonic anhydrase I and II, and xanthine oxidase. All compounds inhibited both enzymes more effectively than standard drugs, acetazolamide and allopurinol, respectively. The biological evaluation results showed that ionic and water soluble coumarin derivatives are promising structures for further investigations especially on enzyme inhibition field.

Synthesis, biological evaluation and molecular docking studies of bis-chalcone derivatives as xanthine oxidase inhibitors and anticancer agents.

In this study, a series of B-ring fluoro substituted bis-chalcone derivatives were synthesized by Claisen-Schmidt condensation reactions and evaluated for their ability to inhibit xanthine oxidase (XO) and growth inhibitory activity against MCF-7 and Caco-2 human cancer cell lines, in vitro. According to the results obtained, the bis-chalcone with fluoro group at the 2 (4b) or 2,5-position (4g) of B-ring were found to be potent inhibitors of the enzyme with IC50 values in the low micromolar range. The effects of these compounds were about 7 fold higher than allopurinol. The binding modes of the bis-chalcone derivatives in the active site of xanthine oxidase were explained using molecular docking calculations. Also, compound 4g and 4h showed in vitro growth inhibitory activity against a panel of two human cancer cell lines 1.9 and 6.8 µM of IC50 values, respectively.

Fast Curing Multifunctional Tissue Adhesives of Sericin-Based Polyurethane-Acrylates for Sternal Closure.

The use of wire cerclage after sternal closure is the standard method because of its rigidity and strength. Despite this, they have many disadvantages such as tissue trauma, operator-induced failures, and the risk of infection. To avoid complications during sternotomy and promote tissue regeneration, tissue adhesives should be used in post-surgical treatment. Here, we report a highly biocompatible, biomimetic, biodegradable, antibacterial, and UV-curable polyurethane-acrylate (PU-A) tissue adhesive for sternal closure as a supportive to wire cerclage. In the study, PU-As were synthesized with variable biocompatible monomers, such as silk sericin, polyethylene glycol, dopamine, and an aliphatic isocyanate 4,4'-methylenebis(cyclohexyl isocyanate). The highest adhesion strength was found to be 4322 kPa, and the ex vivo compressive test result was determined as 715 kPa. The adhesive was determined to be highly biocompatible (on L-929 cells), biodegradable, and antibacterial (on Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus bacteria). Finally, after opening the sternum of rats, the adhesive was applied to bond the bones and cured with UV for 5 min. According to the results, there was no visible inflammation in the adhesive groups, while some animals had high inflammation in the cyanoacrylate and wire cerclage groups. These results indicate that the adhesive may be suitable for sternal fixation by preventing the disadvantages of the steel wires and promoting tissue healing.

Photocrosslinkable gelatin/collagen based bioinspired polyurethane-acrylate bone adhesives with biocompatibility and biodegradability.

Hard or soft tissue adhesives have been presented as a promising candidate to replace traditional wound closure methods. However, there are mechanical strength problems in biological adhesives and biocompatibility problems in synthetic-based adhesives. At this point, we aimed to remove all these disadvantages and produce a single adhesive that contains all the necessary features and acrylate functionalized UV-curable polyurethane formulations were produced with high crosslink density, high adhesion strength, biocompatibility and injectable property for easy application as potential biomedical adhesives. Aliphatic isophorone diisocyanate (IPDI) was used as the isocyanate source and ß-cyclodextrin was used for host-guest relationship with gentamicin by crosslinking. Proteins (gelatin (GEL), collagen (COL)) and PEGs of various molecular weight ranges (P200, P400, P600) were selected as the polyol backbone for polyurethane synthesis due to their multiple biological activities such as biocompatibility, biodegradability, biomimetic property. Several techniques have been used to characterize the structural, thermal, morphological, and various other physicochemical properties of the adhesive formulations. Besides, the possibility of its use as a hard tissue adhesive was investigated by evaluating the tissue adhesion strength in vitro and ex vivo via a universal testing analyzer in tensile mode. Corresponding adhesive formulations were evaluated by in vitro and in vivo techniques for biocompatibility. The best adhesion strength results were obtained as 3821.0 ±â€¯214.9, and 3722.2 ±â€¯486.8 kPa, for IPDI-COL-P200 and IPDI-GEL-P200, respectively. Good antibacterial activity capability toward Escherichia coli Pseudomonas aeruginosa, and Staphylococcus aureus were confirmed using disc diffusion method. Moreover, cell viability assay demonstrated that the formulations have no significant cytotoxicity on the L929 fibroblast cells. Most importantly, we finally performed the in vivo biodegradability and in vivo biocompatibility evaluations of the adhesive formulations on rat model. Considering their excellent cell/tissue viability, fast curable, strong adhesion, high antibacterial character, and injectability, these adhesive formulations have significant potential for tissue engineering applications.

Melatonin protects sperm cells of Capoeta trutta from toxicity of titanium dioxide nanoparticles.

In this study, it was aimed to determine the protective effects of melatonin (0.01, 0.1, and 1 mM) against 10 mg/L titanium dioxide nanoparticles (TiO2-NPs) on kinematic and oxidative indices in the sperm cells of Capoeta trutta. Therefore, TiO2 nanoparticles were synthesized primarily within the scope of the study. The synthesized nanoparticles were characterized by structurally different techniques. Then, melatonin and TiO2 were applied to Capoeta trutta sperm cells by in vitro. According to our data, all doses of melatonin showed protective effects on all velocities of sperm cells such as the straight line velocity (VSL), the curvilinear velocity (VCL), and the angular path velocity (VAP) against TiO2-NPs, while 0.1 and 1 mM doses of melatonin improved the VSL value. Although TiO2-NPs increased total glutathione (tGSH), malondialdehyde (MDA) lipid peroxidation, and superoxide dismutase (SOD) compared to the control group, there were positive treatment effects for all doses of melatonin on antioxidant capacity of sperm cells. At the end of this research, it is suggested that over 0.1 mM dose of melatonin improves the velocity of sperm cells and it plays a protective role against the toxic effects of TiO2-NPs.

Investigation of toxic effects of amorphous SiO2 nanoparticles on motility and oxidative stress markers in rainbow trout sperm cells.

In this study, we investigated the effects of SiO2 nanoparticles (SiO2-NPs) (1, 10, 25, 50, and 100 mg/L) for 24 h in vitro on the motility parameters and oxidative stress markers such as total glutathione (TGSH), catalase (CAT), and malondialdehyde (MDA) of rainbow trout, Oncorhynchus mykiss sperm cells. Therefore, SiO2-NPs were synthesized with sol-gel reaction from tetraethoxy orthosilicate (TEOS). The prepared nanoparticle structures were characterized for chemical structure, morphology and thermal behavior employing Fourier transform infrared spectroscopy, X-ray spectroscopy, scanning electron micrograph, and thermal analysis (DTA/TGA/DSC) techniques. After exposure, there was statistically significant (p < 0.05) decreases in velocities of sperm cells. CAT activity significantly (p < 0.05) decreased by 9.6% in sperm cell treated with 100 mg/L. In addition, MDA level significantly increased by 70.4% and 77.5% in sperm cell treated with 50 and 100 mg/L SiO2-NPs, respectively (p < 0.05). These results showed that SiO2-NPs may have toxic effect on rainbow trout sperm cells in 50 mg/L and more.

The Toxicity Assessment of Iron Oxide (Fe3O4) Nanoparticles on Physical and Biochemical Quality of Rainbow Trout Spermatozoon.

The aim of this study was to evaluate the in vitro effect of different doses (50, 100, 200, 400, and 800 mg/L) of Fe3O4 nanoparticles (NPs) at 4 °C for 24 h on the kinematics of rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) spermatozoon. Firstly, Fe3O4 NPs were prepared at about 30 nm from Iron (III) chloride, Iron (II) chloride, and NH3 via a co-precipitation synthesis technique. Then, the prepared Fe3O4 NPs were characterized by different instrumental techniques for their chemical structure, purity, morphology, surface properties, and thermal behavior. The size, microstructure, and morphology of the prepared Fe3O4 NPs were studied by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) spectroscopy, and scanning electron microscopy (SEM) equipped with an energy-dispersive X-ray spectrometer (EDS). The thermal properties of the Fe3O4 NPs were determined with thermogravimetric analysis (TGA), differential thermal analysis (DTA), and differential scanning calorimeter (DSC) analysis techniques. According to our results, there were statistically significant (p < 0.05) decreases in the velocities of spermatozoon after treatment with 400 mg/L Fe3O4 NPs. The superoxide dismutase (SOD) and catalase (CAT) activities were significant (p < 0.05) decrease after 100 mg/L in after exposure to Fe3O4 NPs in 24 h. As the doses of Fe3O4 NPs increases, the level of malondialdehyde (MDA) and total glutathione (tGSH) significantly (p < 0.05) increased at doses of 400 and 800 mg/L.

The in vitro toxicity analysis of titanium dioxide (TiO2) nanoparticles on kinematics and biochemical quality of rainbow trout sperm cells.

In recent years, titanium dioxide (TiO2) nanoparticles (NPs) as metal oxide nanoparticles are widely used in industry, agriculture, personal care products, cosmetics, sun protection and toothpaste, electronics, foodstuffs and food packaging. This use of nano-TiO2 has been associated with environmental toxicity concerns. Therefore, the aim of this study was to evaluate the in vitro effect of different doses of TiO2 NPs (∼30-40 nm) (0.01, 0.1, 0.5, 1, 10 and 50 mg/L) at 4oC for 3 h on the sperm cell kinematics as velocities of Rainbow trout (Oncorhynchus mykiss, Walbaum, 1792) sperm cells. Furthermore, oxidative stress markers (total glutathione (TGSH) and superoxide dismutase (SOD) were assessed in sperm cells after exposure to TiO2 NPs. According to the obtained results, there were statistically significant (P < 0.05) decreasing in the velocities of sperm cells after 10 mg/L TiO2 NPs and an increase the activity of SOD (P < 0.05) and TGSH levels were determined.

Design of Xylose-Based Semisynthetic Polyurethane Tissue Adhesives with Enhanced Bioactivity Properties.

Developing biocompatible tissue adhesives with high adhesion properties is a highly desired goal of the tissue engineering due to adverse effects of the sutures. Therefore, our work involves synthesis, characterization, adhesion properties, protein adsorption, in vitro biodegradation, in vitro and in vivo biocompatibility properties of xylose-based semisynthetic polyurethane (NPU-PEG-X) bioadhesives. Xylose-based semisynthetic polyurethanes were developed by the reaction among 4,4'-methylenebis(cyclohexyl isocyanate) (MCI), xylose and polyethylene glycol 200 (PEG). Synthesized polyurethanes (PUs) showed good thermal stability and high adhesion strength. The highest values in adhesion strength were measured as 415.0 ± 48.8 and 94.0 ± 2.8 kPa for aluminum substrate and muscle tissue in 15% xylose containing PUs (NPU-PEG-X-15%), respectively. The biodegradation of NPU-PEG-X-15% was also determined as 19.96 ± 1.04% after 8 weeks of incubation. Relative cell viability of xylose containing PU was above 86%. Moreover, 10% xylose containing NPU-PEG-X (NPU-PEG-X-10%) sample has favorable tissue response, and inflammatory reaction between 1 and 6 weeks implantation period. With high adhesiveness and biocompatibility properties, NPU-PEG-X can be used in the medical field as supporting materials for preventing the fluid leakage after abdominal surgery or wound closure.