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A series of new unique acetylene derivatives of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonamide 3a - f and 6a - f were prepared by reactions of 8-hydroxy- and 8-methoxyquinoline- 5-sulfonyl chlorides with acetylene derivatives of amine. A series of new hybrid systems containing quinoline and 1,2,3-triazole systems 7a - h were obtained by reactions of acetylene derivatives of quinoline-5-sulfonamide 6a - d with organic azides. The structures of the obtained compounds were confirmed by 1 H and 13 C NMR spectroscopy and HR-MS spectrometry. The obtained quinoline derivatives 3a - f and 6a - f and 1,2,3-triazole derivatives 7a - h were tested for their anticancer and antimicrobial activity. Human amelanotic melanoma cells (C-32), human breast adenocarcinoma cells (MDA-MB-231), and human lung adenocarcinoma cells (A549) were selected as tested cancer lines, while cytotoxicity was investigated on normal human dermal fibroblasts (HFF-1). All the compounds were also tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis . Only the acetylene derivatives of 8-hydroxyquinoline-5-sulfonamide 3a - f were shown to be biologically active, and 8-hydroxy- N -methyl- N -(prop-2-yn-1-yl)quinoline-5-sulfonamide ( 3c ) showed the highest activity against all three cancer lines and MRSA isolates. Its efficacies were comparable to those of cisplatin/doxorubicin and oxacillin/ciprofloxacin. In the non-cancer HFF-1 line, the compound showed no toxicity up to an IC 50 of 100 µM. In additional tests, compound 3c decreased the expression of H3, increased the transcriptional activity of cell cycle regulators (P53 and P21 proteins), and altered the expression of BCL-2 and BAX genes in all cancer lines. The unsubstituted phenolic group at position 8 of the quinoline is the key structural fragment necessary for biological activity.

One of the definitions of chemical biology is that it is a scientific discipline spanning the fields of chemistry, biology, and physics; it primarily involves the application of chemical techniques, tools, analyses, and often compounds (also known as chemical probes), which are produced through synthetic chemistry, in order to study and manipulate biological systems [...].

Nowadays, lipidomics plays a crucial role in the investigation of novel biomarkers of various diseases. Its implementation into the field of clinical analysis led to the identification of specific lipids and/or significant changes in their plasma levels in patients suffering from cancer, Alzheimer's disease, sepsis, and many other diseases and pathological conditions. Profiling of lipids and determination of their plasma concentrations could also be helpful in the case of drug therapy management, especially in combination with therapeutic drug monitoring (TDM). Here, for the first time, a combined approach based on the TDM of colistin, a last-resort antibiotic, and lipidomic profiling is presented in a case study of a critically ill male patient suffering from Pseudomonas aeruginosa -induced pneumonia. Implementation of innovative analytical approaches for TDM (online combination of capillary electrophoresis with tandem mass spectrometry, CZE-MS/MS) and lipidomics (liquid chromatography-tandem mass spectrometry, LC-MS/MS) was demonstrated. The CZE-MS/MS strategy confirmed the chosen colistin drug dosing regimen, leading to stable colistin concentrations in plasma samples. The determined colistin concentrations in plasma samples reached the required minimal inhibitory concentration of 1 μg/mL. The complex lipidomics approach led to monitoring 545 lipids in collected patient plasma samples during and after the therapy. Some changes in specific individual lipids were in good agreement with previous lipidomics studies dealing with sepsis. The presented case study represents a good starting point for identifying particular individual lipids that could correlate with antimicrobial and inflammation therapeutic management.

The search for the ideal metallic material for an implant is still a difficult challenge for scientists due to the phenomenon of corrosion and the consequent disruption of the implant structure. Prevention is the application of coatings that protect the implant, activate the tissues for faster regeneration, and also prevent inflammation through antibacterial and antiviral effects. The present study focuses on the selection of components for a Ti-6Al-4V alloy coating. These days, researchers are taking an intense interest in extracts of natural origin. It was decided to take a look at Sideritis raeseri , which contains vitamins and valuable elements and is rich in polyphenols, as well as antioxidants. The composition of coatings based on a PEG polymer reinforced with brushite and the S. raeseri extract with the proteins L-carnosine, fibroin, or sericin was developed. The samples were subjected to detailed physiochemical analysis, including potentiometry and electrical conductivity analysis, Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD) analysis, and UV-VIS spectroscopy. The study demonstrated that polyphenols were successfully released from the coatings during incubation in vitro. The osteointegration process can be supported by a number of factors, such as the release of polyphenols from implant coatings to prevent bacterial, viral, and fungal infections. Subjecting the samples to 14 days of incubation demonstrated their interactions with the incubation fluids, an ion exchange between the medium and the materials. An analysis of the surface morphology exhibited the presence of brushite crystals and their increased number after incubation, indicating the bioactivity of the formed coatings.

Many biologically active metabolites of the essential amino acid L-tryptophan (Trp) are associated with different neurodegenerative diseases and neurological disorders. Precise and reliable methods for their determination are needed. Variability in their physicochemical properties makes the analytical process challenging. In this case, chemical modification of analyte derivatization could come into play. Here, we introduce a novel fast reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) coupled with tandem mass spectrometry (MS/MS) method for the determination of Trp and its ten metabolites in human plasma samples after derivatization with 2-bromo-4'-nitroacetophenone (BNAP). The derivatization procedure was optimized in terms of incubation time, temperature, concentration, and volume of the derivatization reagent. Method development comprises a choice of a suitable stationary phase, mobile phase composition, and gradient elution optimization. The developed method was validated according to the ICH guidelines. Results of all validation parameters were within the acceptance criteria of the guideline, i.e., intra- and inter-day precision (expressed as relative standard deviation; RSD) were in the range of 0.5-8.2% and 2.3-7.4%, accuracy was in the range of 93.3-109.7% and 94.7-110.1%, limits of detection (LODs) were in the range of 0.15-9.43 ng/mL, coefficients of determination (R2) were higher than 0.9906, and carryovers were, in all cases, less than 8.8%. The practicability of the method was evaluated using the blue applicability grade index (BAGI) with a score of 65. Finally, the developed method was used for the analysis of Alzheimer's disease and healthy control plasma to prove its applicability. Statistical analysis revealed significant changes in picolinic acid (PA), anthranilic acid (AA), 5 hydroxyindole-3-acetic acid (5-OH IAA), and quinolinic acid (QA) concentration levels. This could serve as the basis for future studies that will be conducted with a large cohort of patients.

Targeted therapy represents a real opportunity to improve the health and lives of patients. Developments in this field are confirmed by the fact that the global market for drug carriers was worth nearly $40 million in 2022. For this reason, materials engineering and the development of new drug carrier compositions for targeted therapy has become a key area of research in pharmaceutical drug delivery in recent years. Ceramics, polymers, and metals, as well as composites, are of great interest, as when they are appropriately processed or combined with each other, it is possible to obtain biomaterials for hard tissues, soft tissues, and skin applications. After appropriate modification, these materials can release the drug directly at the site requiring a therapeutic effect. This brief literature review characterizes routes of drug delivery into the body and discusses biomaterials from different groups, options for their modification with clindamycin, an antibiotic used for infections caused by aerobic and anaerobic Gram-positive bacteria, and different methods for the final processing of carriers. Examples of coating materials for skin wound healing, acne therapy, and bone tissue fillers are given. Furthermore, the reasons why the use of antibiotic therapy is crucial for a smooth and successful recovery and the risks of bacterial infections are explained. It was demonstrated that there is no single proven delivery scheme, and that the drug can be successfully released from different carriers depending on the destination.

A series of nine 2,3-disubstituted-quinazolin-4(3 H )-one derived Schiff bases and their three Cu(II) complexes was prepared and tested for their antimicrobial activities against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the substances were tested in vitro against Mycobacterium tuberculosis H 37 Ra ATCC 25177, M. kansasii DSM 44162 and M. smegmatis ATCC 700084. While anti-enterococcal and antimycobacterial activities were insignificant, 3-[( E )-(2-hydroxy-5-nitrobenzylidene)amino]-2-(2-hydroxy-5-nitrophenyl)-2,3-dihydroquinazolin-4(1 H )-one ( SB3 ) and its Cu(II) complex ( SB3-Cu ) demonstrated bacteriostatic antistaphylococcal activity. In addition, both compounds, as well as the other two prepared complexes, showed antibiofilm activity, which resulted in a reduction of biofilm formation and eradication of mature S. aureus biofilm by 80% even at concentrations lower than the values of their minimum inhibitory concentrations. In addition, the compounds were tested for their cytotoxic effect on the human monocytic leukemia cell line THP-1. The antileukemic efficiency was improved by the preparation of Cu(II) complexes from the corresponding non-chelated Schiff base ligands., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Coating materials offers an intriguing solution for imparting inert implants with additional bioactive characteristics without changing underlying parameters such as mechanical strength. Metallic implants like endoprostheses or polymeric implants can be coated with a thin layer of bioactive film capable of stimulating bone-forming cells to proliferate or release a drug. However, irrespective of the final implantation site of such a coating biomaterial, it is necessary to conduct detailed mechanical and physicochemical in vitro analyses to determine its likely behavior under biological conditions. In this study, polymeric and composite coatings with hydroxyapatite obtained under UV light underwent incubation tests in four different artificial biological fluids: simulated body fluid (SBF), artificial saliva, Ringer's fluid, and water (as the reference fluid). The potentiometric and conductometric properties, sorption capacity, and degradation rate of the coatings were examined. Furthermore, their hardness, modulus of elasticity, and deformation were determined. It was demonstrated that the coatings remained stable in SBF liquid at a pH value of around 7.4. In artificial saliva, the greatest degradation of the polymer matrix (ranging between 36.19% and 39.79%) and chipping of hydroxyapatite in the composite coatings were observed. Additionally, the effect of ceramics on sorption capacity was determined, with lower capacity noted with higher HA additions. Moreover, the evaluation of surface morphology supported by elemental microanalysis confirmed the appearance of new apatite layers on the surface as a result of incubation in SBF. Ceramics also influenced mechanical aspects, increasing hardness and modulus of elasticity. For the polymer coatings, the value was 11.48 ± 0.61, while for the composite coating with 15% ceramics, it increased more than eightfold to a value of 93.31 ± 11.18 N/mm 2 . Based on the conducted studies, the effect of ceramics on the physicochemical as well as mechanical properties of the materials was determined, and their behavior in various biological fluids was evaluated. However, further studies, especially cytotoxicity analyses, are required to determine the potential use of the coatings as biomaterials.

Lipids represent a large group of biomolecules that are responsible for various functions in organisms. Diseases such as diabetes, chronic inflammation, neurological disorders, or neurodegenerative and cardiovascular diseases can be caused by lipid imbalance. Due to the different stereochemical properties and composition of fatty acyl groups of molecules in most lipid classes, quantification of lipids and development of lipidomic analytical techniques are problematic. Identification of different lipid species from complex matrices is difficult, and therefore individual analytical steps, which include extraction, separation, and detection of lipids, must be chosen properly. This review critically documents recent strategies for lipid analysis from sample pretreatment to instrumental analysis and data interpretation published in the last five years (2019 to 2023). The advantages and disadvantages of various extraction methods are covered. The instrumental analysis step comprises methods for lipid identification and quantification. Mass spectrometry (MS) is the most used technique in lipid analysis, which can be performed by direct infusion MS approach or in combination with suitable separation techniques such as liquid chromatography or gas chromatography. Special attention is also given to the correct evaluation and interpretation of the data obtained from the lipid analyses. Only accurate, precise, robust and reliable analytical strategies are able to bring complex and useful lipidomic information, which may contribute to clarification of some diseases at the molecular level, and may be used as putative biomarkers and/or therapeutic targets., Competing Interests: The authors declare no conflicts of interest.

In an increasingly aging society, there is a growing demand for the development of technology related to tissue regeneration. It involves the development of the appropriate biomaterials whose properties will allow the desired biological response to be obtained. Bioactivity is strongly affected by the proper selection of active ingredients. The aim of this study was to produce bioactive hydrogel materials based on hyaluronic acid and collagen modified by the addition of placenta. These materials were intended for use as dressings, and their physicochemical properties were investigated under simulated biological environmental conditions. The materials were incubated in vitro in different fluids simulating the environment of the human body (e.g., simulated body fluid) and then stored at a temperature close to body temperature. Using an FT-IR spectrophotometer, the functional groups present in the composites were identified. The materials with the added placenta showed an increase in the swelling factor of more than 300%. The results obtained confirmed the potential of using this material as an absorbent dressing. This was indicated by pH and conductometric measurements, sorption, degradation, and surface analysis under an optical microscope. The results of the in vitro biological evaluation confirmed the cytosafety of the tested biomaterials. The tested composites activate monocytes, which may indicate their beneficial properties in the first phases of wound healing. The material proved to be nontoxic and has potential for medical use.

In recent years, significant developments have taken place in scientific fields such as tissue and materials engineering, which allow for the development of new, intelligent biomaterials. An example of such biomaterials is drug delivery systems that release the active substance directly at the site where the therapeutic effect is required. In this research, polymeric materials and ceramic-polymer composites were developed as carriers for the antibiotic clindamycin. The preparation and characterization of biomaterials based on hyaluronic acid, collagen, and nano brushite obtained using the photocrosslinking technique under UV (ultraviolet) light are described. Physical and chemical analyses of the materials obtained were carried out using Fourier transform infrared spectroscopy (FT-IR) and optical microscopy. The sorption capacities were determined and subjected to in vitro incubation in simulated biological environments such as Ringer's solution, simulated body fluid (SBF), phosphate-buffered saline (PBS), and distilled water. The antibiotic release rate was also measured. The study confirmed higher swelling capacity for materials with no addition of a ceramic phase, thus it can be concluded that brushite inhibits the penetration of the liquid medium into the interior of the samples, leading to faster absorption of the liquid medium. In addition, incubation tests confirmed preliminary biocompatibility. No drastic changes in pH values were observed, which suggests that the materials are stable under these conditions. The release rate of the antibiotic from the biomaterial into the incubation medium was determined using high-pressure liquid chromatography (HPLC). The concentration of the antibiotic in the incubation fluid increased steadily following a 14-day incubation in PBS, indicating continuous antibiotic release. Based on the results, it can be concluded that the developed polymeric material demonstrates potential for use as a carrier for the active substance.

In this paper, we describe a new method for synthesizing hybrid combinations of 1,2,3-triazoles with a tetracyclic quinobenzothiazinium system. The developed approach allowed for the production of a series of new azaphenothiazine derivatives with the 1,2,3-triazole system in different positions of the benzene ring. In practice, the methodology consists of the reaction of triazole aniline derivatives with thioquinanthrenediinium bis -chloride. The structure of the products was determined by 1 H-NMR, 13 C-NMR spectroscopy, and HR-MS spectrometry, respectively. Moreover, the spatial structure of the molecule and the arrangement of molecules in the crystal (unit cell) were determined by X-ray crystallography. The anticancer activity profiles of the synthesized compounds were tested in vitro against human cancer cells of the A549, SNB-19, and T47D lines and the normal NHDF cell line. Additional tests of antibacterial activity against methicillin-sensitive and methicillin-resistant staphylococci , vancomycin-sensitive and vancomycin-resistant enterococci , and two mycobacterial strains were also performed. In fact, the dependence of anticancer and antibacterial activity on the substituent type and its position in the quinobenzothiazinium system was observed. Furthermore, the distance-guided property evaluation was performed using principal component analysis (PCA) and hierarchical clustering analysis (HCA) on the pool of the calculated descriptors. Finally, the theoretically approximated partition coefficients (clogP) were (inter-)correlated with each other and cross-compared with the empirically specified logP TLC parameters.

This study aimed to obtain and investigate ZnCr 2 Se 4 single crystals doped with rhenium. The single crystals were obtained by applying chemical vapour transport. An X-ray study confirmed the cubic (Fd3¯m) structure of the tested crystals. Thermal, magnetic, electrical, and specific heat measurements accurately determined the physicochemical characteristics, which revealed that the obtained single crystals are p -type semiconductors with antiferromagnetic order below the Néel temperature T N = 21.7 K. The Debye temperature had a value of 295 K. The substitution of Re-paramagnetic ions, possessing a screened 5 d -shell, in place of Zn-diamagnetic ions, caused an increase in the activation energy, Fermi energy, and Fermi temperature compared to the pure ZnCr 2 Se 4 . The boost of the dc magnetic field induced a shift of T N towards lower temperatures and a spin fluctuation peak visible at H dc = 40 and 50 kOe. The obtained single crystals are thermally stable up to 1100 °C.

Bioactive calcium phosphate ceramics (CaPs) are one of the building components of the inorganic part of bones. Synthetic CaPs are frequently used as materials for filling bone defects in the form of pastes or composites; however, their porous structure allows modification with active substances and, thus, subsequent use as a drug carrier for the controlled release of active substances. In this study, four different ceramic powders were compared: commercial hydroxyapatite (HA), TCP, brushite, as well as HA obtained by wet precipitation methods. The ceramic powders were subjected to physicochemical analysis, including FTIR, XRD, and determination of Ca/P molar ratio or porosity. These techniques confirmed that the materials were phase-pure, and the molar ratios of calcium and phosphorus elements were in accordance with the literature. This confirmed the validity of the selected synthesis methods. CaPs were then modified with the antibiotic clindamycin. Drug release was determined on HPLC, and antimicrobial properties were tested against Staphylococcus aureus . The specific surface area of the ceramic has been demonstrated to be a factor in drug release efficiency.

Twelve drugs containing sildenafil compounds (sildenafil citrate and sildenafil base) were examined using X-ray studies and thermal analysis. According to the manufacturer's information, the presence of sildenafil was confirmed in all investigated drugs. The positions of diffraction lines (value of 2 θ angle) agree with the patterns presented in the ICDD database, Release 2018 (ICDD-International Centre of Diffraction Data). The difference expresses the agreement in the position of the diffraction line between the tested substance and the standard. A good agreement is when this difference is less than 0.2°. The values of interplanar distances d hkl are also compatible with the ICDD database. It indicated that the drug examined was genuine. Because all drugs are mixtures of different substances (API and excipients), the various diffraction line intensities were detected in all observed X-ray images for the tested drugs. The intensity of the diffraction line depends on many factors, like the amount of substance, coexisting phases, and mass absorption coefficient of the mixture. The thermal analysis confirmed the results obtained by the X-ray study. On DSC curves, the endothermic peaks for sildenafil compounds were observed. The determined melting points of sildenafil compounds corresponded to the values available in the literature. The results gathered by connecting two methods, X-ray study and thermal analysis, can help identify irregularities that may exist in pharmaceutical specimens, e.g., distinguishing genuine from counterfeit products, the presence of a correct polymorph, a lack of active substance, an inaccurate amount of the active substance, or excipients in the tested drug.

Conventional intake of drugs and active substances is most often based on oral intake of an appropriate dose to achieve the desired effect in the affected area or source of pain. In this case, controlling their distribution in the body is difficult, as the substance also reaches other tissues. This phenomenon results in the occurrence of side effects and the need to increase the concentration of the therapeutic substance to ensure it has the desired effect. The scientific field of tissue engineering proposes a solution to this problem, which creates the possibility of designing intelligent systems for delivering active substances precisely to the site of disease conversion. The following review discusses significant current research strategies as well as examples of polymeric and composite carriers for protein and non-protein biomolecules designed for bone tissue regeneration.

A series of seventeen 4-chlorocinnamanilides and seventeen 3,4-dichlorocinnamanilides were characterized for their antiplasmodial activity. In vitro screening on a chloroquine-sensitive strain of Plasmodium falciparum 3D7/MRA-102 highlighted that 23 compounds possessed IC 50 < 30 µM. Typically, 3,4-dichlorocinnamanilides showed a broader range of activity compared to 4-chlorocinnamanilides. (2 E )- N -[3,5-bis(trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-en-amide with IC 50 = 1.6 µM was the most effective agent, while the other eight most active derivatives showed IC 50 in the range from 1.8 to 4.6 µM. A good correlation between the experimental log k and the estimated clogP was recorded for the whole ensemble of the lipophilicity generators. Moreover, the SAR-mediated similarity assessment of the novel (di)chlorinated N -arylcinnamamides was conducted using the collaborative (hybrid) ligand-based and structure-related protocols. In consequence, an 'averaged' selection-driven interaction pattern was produced based in namely 'pseudo-consensus' 3D pharmacophore mapping. The molecular docking approach was engaged for the most potent antiplasmodial agents in order to gain an insight into the arginase-inhibitor binding mode. The docking study revealed that (di)chlorinated aromatic (C-phenyl) rings are oriented towards the binuclear manganese cluster in the energetically favorable poses of the chloroquine and the most potent arginase inhibitors. Additionally, the water-mediated hydrogen bonds were formed via carbonyl function present in the new N -arylcinnamamides and the fluorine substituent (alone or in trifluoromethyl group) of N -phenyl ring seems to play a key role in forming the halogen bonds.

This study aimed to evaluate the lipophilicity of a series substances lowering the concentration of uric acid in blood and anti-androgen drugs by thin-layer chromatography in reversed-phase systems (RP-TLC, RP-HPTLC) and computational methods. The chromatographic parameter of lipophilicity (R MW ) of tested compounds was determined on three stationary phases, i.e., RP18F 254 , RP18WF 254 and RP2F 254 , using ethanol-water, propan-2-ol-water and acetonitrile-water in various volume compositions as mobile phases. The chromatographic analysis led to determining the experimental value of the lipophilicity parameter for each of the tested compounds, including those for which the experimental value of the partition coefficient (logP exp ) as a measure of lipophilicity is not well described in available databases, such as febuxostat, oxypurinol, ailanthone, abiraterone and teriflunomide. The chromatographic parameters of lipophilicity were compared with the logP values obtained with various software packages, such as AClogP, AlogPs, AlogP, MlogP, XlogP2, XlogP3, ACD/logP and logP KOWWIN . The obtained results indicate that, among selected chromatographic parameters of lipophilicity, both experimental and calculated logP values gave similar results, and these RP-TLC or RP-HPTLC systems can be successfully applied to estimate the lipophilicity of studied heterocyclic compounds belonging to two different pharmacological groups. This work also illustrates the similarity and difference existing between the tested compounds under study using the chemometric methods, such as principal component analysis (PCA) and cluster analysis (CA). In addition, a relatively new approach based on the sum of ranking differences (SRD) was used to compare the chromatographically obtained and theoretical lipophilicity descriptors of studied compounds.

According to the WHO, cancer caused almost 10 million deaths worldwide in 2020, i.e., almost one in six deaths. Among the most common are breast, lung, colon and rectal and prostate cancers. Although the diagnosis is more perfect and spectrum of available drugs is large, there is a clear trend of an increase in cancer that ends fatally. A major advance in treatment was the introduction of gentler antineoplastics for targeted therapy-tyrosine kinase inhibitors (TKIs). Although they have undoubtedly revolutionized oncology and hematology, they have significant side effects and limited efficacy. In addition to the design of new TKIs with improved pharmacokinetic and safety profiles, and being more resistant to the development of drug resistance, high expectations are placed on the reformulation of TKIs into various drug delivery lipid-based nanosystems. This review provides an insight into the history of chemotherapy, a brief overview of the development of TKIs for the treatment of cancer and their mechanism of action and summarizes the results of the applications of self-nanoemulsifying drug delivery systems, nanoemulsions, liposomes, solid lipid nanoparticles, lipid-polymer hybrid nanoparticles and nanostructured lipid carriers used as drug delivery systems of TKIs obtained in vitro and in vivo.

The use of natural compounds is becoming increasingly popular among patients, and there is a renewed interest among scientists in nature-based bioactive agents. Traditionally, herbal drugs can be taken directly in the form of teas/decoctions/infusions or as standardized extracts. However, the disadvantages of natural compounds, especially essential oils, are their instability, limited bioavailability, volatility, and often irritant/allergenic potential. However, these active substances can be stabilized by encapsulation and administered in the form of nanoparticles. This brief overview summarizes the latest results of the application of nanoemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers used as drug delivery systems of herbal essential oils or used directly for their individual secondary metabolites applicable in cancer therapy. Although the discussed bioactive agents are not typical compounds used as anticancer agents, after inclusion into the aforesaid formulations improving their stability and bioavailability and/or therapeutic profile, they indicated anti-tumor activity and became interesting agents with cancer treatment potential. In addition, co-encapsulation of essential oils with synthetic anticancer drugs into nanoformulations with the aim to achieve synergistic effect in chemotherapy is discussed.

A new method for modifying the structure of tetracyclic quinobenzothiazinium derivatives has been developed, allowing introduction of various substituents at different positions of the benzene ring. The method consists of reacting appropriate aniline derivatives with 5,12-(dimethyl)thioquinantrenediinium bis-chloride. A series of new quinobenzothiazine derivatives was obtained with propyl, allyl, propargyl and benzyl substituents in 9, 10 and 11 positions, respectively. The structure of the obtained compounds was analyzed by 1H and 13C NMR (HSQC, HMBC) and X-ray analysis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212, and representatives of multidrug-resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). In addition, all the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. 9-Benzyloxy-5-methyl-12H-quino [3,4-b][1,4]benzothiazinium chloride (6j), 9-propoxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6a) and 9-allyloxy-5-methyl-12H-quino[3,4-b][1,4]benzothiazinium chloride (6d) demonstrated high activity against the entire tested microbial spectrum. The activities of the compounds were comparable with oxacillin, tetracycline and ciprofloxacinagainst staphylococcal strains and with rifampicin against both mycobacterial strains. Compound 6j had a significant effect on the inhibition of bacterial respiration as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity, but also bactericidal activity. Preliminary in vitro cytotoxicity screening of the compounds performed using normal human dermal fibroblasts (NHDF) proved that the tested compounds showed an insignificant cytotoxic effect on human cells (IC50 > 37 µM), making these compounds interesting for further investigation. Moreover, the intermolecular similarity of novel compounds was analyzed in the multidimensional space (mDS) of the structure/property-related in silico descriptors by means of principal component analysis (PCA) and hierarchical clustering analysis (HCA), respectively. The distance-oriented structure/property distribution was related with the experimental lipophilic data.

A series of thirty-two anilides of 3-(trifluoromethyl)cinnamic acid (series 1 ) and 4-(trifluoromethyl)cinnamic acid (series 2 ) was prepared by microwave-assisted synthesis. All the compounds were tested against reference strains Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 and resistant clinical isolates of methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecalis (VRE). All the compounds were evaluated in vitro against Mycobacterium smegmatis ATCC 700084 and M. marinum CAMP 5644. (2 E )-3-[3-(Trifluoromethyl)phenyl]- N -[4-(trifluoromethyl)phenyl]prop-2-enamide ( 1j ), (2 E )- N -(3,5-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide ( 1o ) and (2 E )- N -[3-(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)-phenyl]prop-2-enamide ( 2i ), (2 E )- N -[3,5-bis(trifluoromethyl)phenyl]-3-[4-(trifluoromethyl)phenyl]-prop-2-enamide ( 2p ) showed antistaphylococcal (MICs/MBCs 0.15-5.57 µM) as well as anti-enterococcal (MICs/MBCs 2.34-44.5 µM) activity. The growth of M. marinum was strongly inhibited by compounds 1j and 2p in a MIC range from 0.29 to 2.34 µM, while all the agents of series 1 showed activity against M. smegnatis (MICs ranged from 9.36 to 51.7 µM). The performed docking study demonstrated the ability of the compounds to bind to the active site of the mycobacterial enzyme InhA. The compounds had a significant effect on the inhibition of bacterial respiration, as demonstrated by the MTT assay. The compounds showed not only bacteriostatic activity but also bactericidal activity. Preliminary in vitro cytotoxicity screening was assessed using the human monocytic leukemia cell line THP-1 and, except for compound 2p , all effective agents did show insignificant cytotoxic effect. Compound 2p is an interesting anti-invasive agent with dual (cytotoxic and antibacterial) activity, while compounds 1j and 1o are the most interesting purely antibacterial compounds within the prepared molecules.

Due to the urgent need of innovation in the antimalarial therapeutic arsenal, a series of thirty-seven ring-substituted N -arylcinnamanilides prepared by microwave-assisted synthesis were subjected to primary screening against the chloroquine-sensitive strain of P. falciparum 3D7/MRA-102. The lipophilicity of all compounds was experimentally determined as the logarithm of the capacity factor k , and these data were subsequently used in the discussion of structure-activity relationships. Among the screened compounds, fourteen derivatives exhibited IC 50 from 0.58 to 31 µM, whereas (2 E )- N -(4-bromo-2-chlorophenyl)-3-phenylprop-2-enamide ( 24 ) was the most effective agent (IC 50 = 0.58 µM). In addition, (2 E )- N -[2,6-dibromo-4-(trifluoromethyl)- phenyl]-3-phenylprop-2-enamide ( 36 ), (2 E )- N -[4-nitro-3-(trifluoromethyl)phenyl]-3-phenylprop- 2-enamide ( 18 ), (2 E )- N -(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide ( 23 ), and (2 E )-3-phenyl- N -(3,4,5-trichlorophenyl)prop-2-enamide ( 33 ) demonstrated efficacy in the IC 50 range from 2.0 to 4.3 µM, comparable to the clinically used standard chloroquine. The results of a cell viability screening performed using THP1-Blue™ NF-κB cells showed that none of these highly active compounds displayed any significant cytotoxic effect up to 20 μM, which makes them promising Plasmodium selective substances for further investigations.

A series of eleven benzylated intermediates and eleven target compounds derived from salicylanilide were tested against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 as reference strains and against three clinical isolates of methicillin-resistant S. aureus (MRSA) and three isolates of vancomycin-resistant E. faecalis. In addition, the compounds were evaluated against Mycobacterium tuberculosis H37Ra and M. smegmatis ATCC 700084. The in vitro cytotoxicity of the compounds was assessed using the human monocytic leukemia cell line THP-1. The lipophilicity of the prepared compounds was experimentally determined and correlated with biological activity. The benzylated intermediates were found to be completely biologically inactive. Of the final eleven compounds, according to the number of amide groups in the molecule, eight are diamides, and three are triamides that were inactive. 5-Chloro-2-hydroxy-N-[(2S)- 4-(methylsulfanyl)-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino}butan-2-yl]benzamide (3e) and 5-chloro-2-hydroxy-N-[(2S)-(4-methyl-1-oxo-1-{[4-(trifluoromethyl)phenyl]amino)pentan-2-yl)benzamide (3f) showed the broadest spectrum of activity against all tested species/isolates comparable to the used standards (ampicillin and isoniazid). Six diamides showed high antistaphylococcal activity with MICs ranging from 0.070 to 8.95 μM. Three diamides showed anti-enterococcal activity with MICs ranging from 4.66 to 35.8 μM, and the activities of 3f and 3e against M. tuberculosis and M. smegmatis were MICs of 18.7 and 35.8 μM, respectively. All the active compounds were microbicidal. It was observed that the connecting linker between the chlorsalicylic and 4-CF3-anilide cores must be substituted with a bulky and/or lipophilic chain such as isopropyl, isobutyl, or thiabutyl chain. Anticancer activity on THP-1 cells IC50 ranged from 1.4 to >10 µM and increased with increasing lipophilicity.

Monocrystalline chalcogenide spinels ZnCr 2 Se 4 are antiferromagnetic and semiconductor materials. They can be used to dope or alloy with related semiconducting spinels. Therefore, their Pb-doped display is expected to have unique properties and new potential applications. This paper presents the results of dc and ac magnetic measurements, including the critical fields visible on the magnetisation isotherms, electrical conductivity, and specific heat of the ZnCr 2 S 4 :Pb single crystals. These studies showed that substituting the diamagnetic Pb ion with a large ion radius for the Zn one leads to strong short-range ferromagnetic interactions in the entire temperature range and spin fluctuations in the paramagnetic region at H dc = 50 kOe.

Pattern 1-hydroxy-N-(2,4,5-trichlorophenyl)-2-naphthamide and the thirteen original carbamates derived from it were prepared and characterized. All the compounds were tested against Staphylococcus aureus ATCC 29213 as a reference and quality control strain and in addition against three clinical isolates of methicillin-resistant S. aureus (MRSA). Moreover, the compounds were evaluated against Enterococcus faecalis ATCC 29212, and preliminary in vitro cytotoxicity of the compounds was assessed using the human monocytic leukemia cell line (THP-1). The lipophilicity of the prepared compounds was experimentally determined and correlated with biological activity. While pattern anilide had no antibacterial activity, the prepared carbamates demonstrated high antistaphylococcal activity comparable to the used standards (ampicillin and ciprofloxacin), which unfortunately were ineffective against E. feacalis. 2-[(2,4,5-Trichlorophenyl)carba- moyl]naphthalen-1-yl ethylcarbamate (2) and 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl butylcarbamate (4) expressed the nanomolar minimum inhibitory concentrations (MICs 0.018−0.064 μM) against S. aureus and at least two other MRSA isolates. Microbicidal effects based on the minimum bactericidal concentrations (MBCs) against all the tested staphylococci were found for nine carbamates, while 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl heptylcarbamate (7) and 2-[(2,4,5-trichlorophenyl)carbamoyl]naphthalen-1-yl (4-phenylbutyl)carbamate (14) demonstrated MBCs in the range of 0.124−0.461 μM. The selectivity index (SI) for most investigated carbamates was >20 and for some derivatives even >100. The performed tests did not show an effect on the damage to the bacterial membrane, while the compounds were able to inhibit the respiratory chain of S. aureus.

Climate change and increasing contamination of the environment, due to anthropogenic activities, are accompanied with a growing negative impact on human life. Nowadays, humanity is threatened by the increasing incidence of difficult-to-treat cancer and various infectious diseases caused by resistant pathogens, but, on the other hand, ensuring sufficient safe food for balanced human nutrition is threatened by a growing infestation of agriculturally important plants, by various pathogens or by the deteriorating condition of agricultural land. One way to deal with all these undesirable facts is to try to develop technologies and sophisticated materials that could help overcome these negative effects/gloomy prospects. One possibility is to try to use nanotechnology and, within this broad field, to focus also on the study of two-dimensional carbon-based nanomaterials, which have excellent prospects to be used in various economic sectors. In this brief up-to-date overview, attention is paid to recent applications of graphene-based nanomaterials, i.e., graphene, graphene quantum dots, graphene oxide, graphene oxide quantum dots, and reduced graphene oxide. These materials and their various modifications and combinations with other compounds are discussed, regarding their biomedical and agro-ecological applications, i.e., as materials investigated for their antineoplastic and anti-invasive effects, for their effects against various plant pathogens, and as carriers of bioactive agents (drugs, pesticides, fertilizers) as well as materials suitable to be used in theranostics. The negative effects of graphene-based nanomaterials on living organisms, including their mode of action, are analyzed as well.

Microbial infections caused by a variety of drug-resistant microorganisms are more common, but there are fewer and fewer approved new antimicrobial chemotherapeutics for systemic administration capable of acting against these resistant infectious pathogens. Formulation innovations of existing drugs are gaining prominence, while the application of nanotechnologies is a useful alternative for improving/increasing the effect of existing antimicrobial drugs. Nanomaterials represent one of the possible strategies to address this unfortunate situation. This review aims to summarize the most current results of nanoformulations of antibiotics and antibacterial active nanomaterials. Nanoformulations of antimicrobial peptides, synergistic combinations of antimicrobial-active agents with nitric oxide donors or combinations of small organic molecules or polymers with metals, metal oxides or metalloids are discussed as well. The mechanisms of actions of selected nanoformulations, including systems with magnetic, photothermal or photodynamic effects, are briefly described.

A series of eighteen 4-chlorocinnamanilides and eighteen 3,4-dichlorocinnamanilides were designed, prepared and characterized. All compounds were evaluated for their activity against gram-positive bacteria and against two mycobacterial strains. Viability on both cancer and primary mammalian cell lines was also assessed. The lipophilicity of the compounds was experimentally determined and correlated together with other physicochemical properties of the prepared derivatives with biological activity. 3,4-Dichlorocinnamanilides showed a broader spectrum of action and higher antibacterial efficacy than 4-chlorocinnamanilides; however, all compounds were more effective or comparable to clinically used drugs (ampicillin, isoniazid, rifampicin). Of the thirty-six compounds, six derivatives showed submicromolar activity against Staphylococcus aureus and clinical isolates of methicillin-resistant S. aureus (MRSA). (2 E )- N -[3,5-bis(trifluoromethyl)phenyl]- 3-(4-chlorophenyl)prop-2-enamide was the most potent in series 1 . (2 E )- N -[3,5-bis(Trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-enamide, (2 E )-3-(3,4-dichlorophenyl)- N -[3-(trifluoromethyl)phenyl]prop-2-enamide, (2 E )-3-(3,4-dichloro- phenyl)- N -[4-(trifluoromethyl)phenyl]prop-2-enamide and (2 E )-3-(3,4-dichlorophenyl)- N -[4-(trifluoromethoxy)phenyl]prop-2-enamide were the most active in series 2 and in addition to activity against S. aureus and MRSA were highly active against Enterococcus faecalis and vancomycin-resistant E. faecalis isolates and against fast-growing Mycobacterium smegmatis and against slow-growing M. marinum , M. tuberculosis non-hazardous test models. In addition, the last three compounds of the above-mentioned showed insignificant cytotoxicity to primary porcine monocyte-derived macrophages.

X-ray powder diffraction (XRPD) and thermal analysis (differential scanning calorimetry/derivative of thermogravimetry (DSC/DTG)) are solid-state techniques that can be successfully used to identify and quantify various chemical compounds in polycrystalline mixtures, such as dietary supplements or drugs. In this work, 31 dietary supplements available on the Polish market that contain iron compounds, namely iron gluconate, fumarate, bisglycinate, citrate and pyrophosphate, were evaluated. The aim of the work was to identify iron compounds declared by the manufacturer as food supplements and to try to verify compliance with the manufacturer's claims. Studies performed by X-ray and thermal analysis confirmed that crystalline iron compounds (iron (II) gluconate, iron (II) fumarate), declared by the manufacturers, were present in the investigated dietary supplements. Iron (II) bisglycinate proved to be semi-crystalline. However, depending on the composition of the formulation, it was possible to identify this compound in the tested supplements. For amorphous iron compounds (iron (III) citrate and iron (III) pyrophosphate), the diffraction pattern does not have characteristic diffraction lines. Food supplements containing crystalline iron compounds have a melting point close to the melting point of pure iron compounds. The presence of excipients was found to affect the shapes and positions of the endothermic peaks significantly. Widening of endothermic peaks and changes in their position were observed, as well as exothermic peaks indicating crystallization of amorphous compounds. Weight loss was determined for all dietary supplements tested. Analysis of the DTG curves showed that the thermal decomposition of most food supplements takes place in several steps. The results obtained by a combination of both simple, relatively fast and reliable XRPD and DSC/DTG methods are helpful in determining phase composition, pharmaceutical abnormalities or by detecting the presence of the correct polymorphic form.

A series of new tertiary phenothiazine derivatives containing a quinoline and a pyridine fragment was synthesized by the reaction of 1-methyl-3-benzoylthio-4-butylthioquinolinium chloride with 3-aminopyridine derivatives bearing various substituents on the pyridine ring. The direction and mechanism of the cyclization reaction of intermediates with the structure of 1-methyl-4-(3-pyridyl)aminoquinolinium-3-thiolate was related to the substituents in the 2- and 4-pyridine position. The structures of the compounds were analyzed using 1 H, 13 C NMR (COSY, HSQC, HMBC) and X-ray analysis, respectively. Moreover, the antiproliferative activity against tumor cells (A549, T47D, SNB-19) and a normal cell line (NHDF) was tested. The antibacterial screening of all the compounds was conducted against the reference and quality control strain Staphylococcus aureus ATCC 29213, three clinical isolates of methicillin-resistant S. aureus (MRSA). In silico computation of the intermolecular similarity was performed using principal component analysis (PCA) and hierarchical clustering analysis (HCA) on the pool of structure/property-related descriptors calculated for the novel tetracyclic diazaphenothiazine derivatives. The distance-oriented property evaluation was correlated with the experimental anticancer activities and empirical lipophilicity as well. The quantitative shape-based comparison was conducted using the CoMSA method in order to indicate the potentially valid steric, electronic and lipophilic properties. Finally, the numerical sampling of similarity-related activity landscape (SALI) provided a subtle picture of the SAR trends.

Since the worldwide incidence of bone disorders and cartilage damage has been increasing and traditional therapy has reached its limits, nanomaterials can provide a new strategy in the regeneration of bones and cartilage. The nanoscale modifies the properties of materials, and many of the recently prepared nanocomposites can be used in tissue engineering as scaffolds for the development of biomimetic materials involved in the repair and healing of damaged tissues and organs. In addition, some nanomaterials represent a noteworthy alternative for treatment and alleviating inflammation or infections caused by microbial pathogens. On the other hand, some nanomaterials induce inflammation processes, especially by the generation of reactive oxygen species. Therefore, it is necessary to know and understand their effects in living systems and use surface modifications to prevent these negative effects. This contribution is focused on nanostructured scaffolds, providing a closer structural support approximation to native tissue architecture for cells and regulating cell proliferation, differentiation, and migration, which results in cartilage and bone healing and regeneration.

The results presented in this paper confirm the beneficial role of an easy-to-use and low-cost thin-layer chromatography (TLC) technique for describing the retention behavior and the experimental lipophilicity parameter of two biguanide derivatives, metformin and phenformin, in both normal-phase (NP) and reversed-phase (RP) TLC systems. The retention parameters (R F , R M ) obtained under different chromatographic conditions, i.e., various stationary and mobile phases in the NP-TLC and RP-TLC systems, were used to determine the lipophilicity parameter (R MW ) of metformin and phenformin. This study confirms the poor lipophilicity of both metformin and phenformin. It can be stated that the optimization of chromatographic conditions, i.e., the kind of stationary phase and the composition of mobile phase, was needed to obtain the reliable value of the chromatographic lipophilicity parameter (R MW ) in this study. The fewer differences in the R MW values of both biguanide derivatives were ensured by the RP-TLC system composed of RP2, RP18, and RP18W plates and the mixture composed of methanol, propan-1-ol, and acetonitrile as an organic modifier compared to the NP-TLC analysis. The new calculation procedures for logP of drugs based on topological indices 0 χ ν , 0 χ, 1 χ ν , M, and M ν may be a certain alternative to other algorithms as well as the TLC procedure performed under optimized chromatographic conditions. The knowledge of different lipophilicity parameters of the studied biguanides can be useful in the future design of novel and more therapeutically effective metformin and phenformin formulations for antidiabetic and possible anticancer treatment. Moreover, the topological indices presented in this work may be further used in the QSAR study of the examined biguanides.

Recently, there has been great interest in the application of polysaccharides in the preparation of diverse biomaterials which result from their biocompatibility, biodegradability and biological activity. In this work, the investigations on chitosan/poly(aspartic acid)-based hydrogels modified with starch were described. Firstly, a series of hydrogel matrices was prepared and investigated to characterize their swelling properties, structure via FT-IR spectroscopy, elasticity and tensile strength using the Brookfield texture analyzer as well as their impact on simulated physiological liquids. Hydrogels consisting of chitosan and poly(aspartic acid) in a 2:1 volume ratio were elastic (9% elongation), did not degrade after 30-day incubation in simulated physiological liquids, exhibited a relative biocompatibility towards these liquids and similar swelling in each absorbed medium. This hydrogel matrix was modified with starch wherein two of its form were applied-a solution obtained at an elevated temperature and a suspension obtained at room temperature. Hydrogels modified with hot starch solution showed higher sorption that unmodified materials. This was probably due to the higher starch inclusion (i.e., a larger number of hydrophilic groups able to interact with the adsorbed liquid) when this polysaccharide was given in the form of a hot solution. Hydrogels modified with a cold starch suspension had visible heterogeneous inequalities on their surfaces and this modification led to the obtainment materials with unrepeatable structures which made the analysis of their properties difficult and may have led to misleading conclusions.

A set of twenty-four 3-hydroxynaphthalene-2-carboxanilides, disubstituted on the anilide ring by combinations of methoxy/methyl/fluoro/chloro/bromo and ditrifluoromethyl groups at different positions, was prepared. The compounds were tested for their ability to inhibit photosynthetic electron transport (PET) in spinach ( Spinacia oleracea L.) chloroplasts. N -(3,5-Difluorophenyl)-, N -(3,5-dimethylphenyl)-, N -(2,5-difluorophenyl)- and N -(2,5-dimethylphenyl)-3-hydroxynaphthalene-2-carboxamides showed the highest PET-inhibiting activity (IC 50 ~ 10 µM) within the series. These compounds were able to inhibit PET in photosystem II. It has been found that PET-inhibiting activity strongly depends on the position of the individual substituents on the anilide ring and on the lipophilicity of the compounds. The electron-withdrawing properties of the substituents contribute towards the PET activity of these compounds.

The new series of single-crystalline chromium selenides, Ta-doped ZnCr 2 Se 4 , was synthesised by a chemical vapour transport method to determine the impact of a dopant on the structural and thermodynamic properties of the parent compound. We present comprehensive investigations of structural, electrical transport, magnetic, and specific heat properties. It was expected that a partial replacement of Cr ions by a more significant Ta one would lead to a change in direct magnetic interactions between Cr magnetic moments and result in a change in the magnetic ground state and electric transport properties of the ZnCr 2-x Ta x Se 4 ( x = 0.05, 0.06, 0.07, 0.08, 0.1, 0.12) system. We found that all the elements of the cubic system had a cubic spinel structure; however, the doping gain linearly increased the ZnCr 2 -x Ta x Se 4 unit cell volume. Doping with tantalum did not significantly change the semiconductor and magnetic properties of ZnCr 2 Se 4 . For all studied samples (0 ≤ x ≤ 0.12), an antiferromagnetic order (AFM) below T N ~22 K was observed. However, a small amount of Ta significantly reduced the second critical field ( H c2 ) from 65 kOe for x = 0.0 (ZnCr 2 Se 4 matrix) up to 42.2 kOe for x = 0.12, above which the spin helical system changed to ferromagnetic (FM). The H c 2 reduction can lead to strong competition among AFM and FM interactions and spin frustration, as the specific heat under magnetic fields H < H c 2 shows a strong field decrease in T N .

A library of novel 4-{[(benzyloxy)carbonyl]amino}-2-hydroxybenzoic acid amides was designed and synthesized in order to provide potential acetyl- and butyrylcholinesterase (AChE/BChE) inhibitors; the in vitro inhibitory profile and selectivity index were specified. Benzyl (3-hydroxy-4-{[2-(trifluoromethoxy)phenyl]carbamoyl}phenyl)carbamate was the best AChE inhibitor with the inhibitory concentration of IC 50 = 36.05 µM in the series, while benzyl {3-hydroxy-4-[(2-methoxyphenyl)carbamoyl]phenyl}-carbamate was the most potent BChE inhibitor (IC 50 = 22.23 µM) with the highest selectivity for BChE (SI = 2.26). The cytotoxic effect was evaluated in vitro for promising AChE/BChE inhibitors. The newly synthesized adducts were subjected to the quantitative shape comparison with the generation of an averaged pharmacophore pattern. Noticeably, three pairs of fairly similar fluorine/bromine-containing compounds can potentially form the activity cliff that is manifested formally by high structure-activity landscape index (SALI) numerical values. The molecular docking study was conducted for the most potent AChE/BChE inhibitors, indicating that the hydrophobic interactions were overwhelmingly generated with Gln119, Asp70, Pro285, Thr120, and Trp82 aminoacid residues, while the hydrogen bond (HB)-donor ones were dominated with Thr120. π-stacking interactions were specified with the Trp82 aminoacid residue of chain A as well. Finally, the stability of chosen liganded enzymatic systems was assessed using the molecular dynamic simulations. An attempt was made to explain the noted differences of the selectivity index for the most potent molecules, especially those bearing unsubstituted and fluorinated methoxy group.

Carbon is one of the most abundant elements on Earth. In addition to the well-known crystallographic modifications such as graphite and diamond, other allotropic carbon modifications such as graphene-based nanomaterials and carbon nanotubes have recently come to the fore. These carbon nanomaterials can be designed to help deliver or target drugs more efficiently and to innovate therapeutic approaches, especially for cancer treatment, but also for the development of new diagnostic agents for malignancies and are expected to help combine molecular imaging for diagnosis with therapies. This paper summarizes the latest designed drug delivery nanosystems based on graphene, graphene quantum dots, graphene oxide, reduced graphene oxide and carbon nanotubes, mainly for anticancer therapy.

The synthesis and application of sodium trithiocarbonate (Na 2 CS 3 ) for the treatment of real galvanic wastewater in order to remove heavy metals (Cu, Cd and Zn) was investigated. A Central Composite Design/Response Surface Methodology (CCD/RSM) was employed to optimize the removal of heavy metals from industrial wastewater. Adequacy of approximated data was verified using Analysis of Variance (ANOVA). The calculated coefficients of determination ( R 2 and R 2 adj ) were 0.9119 and 0.8532, respectively. Application of Na 2 CS 3 conjugated with CCD/RSM allowed Cu, Cd and Zn levels to be decreased and, as a consequence, ∑ Cu,Cd,Zn decreased by 99.80%, 97.78%, 99.78%, and 99.69%, respectively, by using Na 2 CS 3 at 533 mg/L and pH 9.7, within 23 min. Implementation of conventional metal precipitation reagents (NaOH, Ca(OH) 2 and CaO) at pH 11 within 23 min only decreased ∑ Cu,Cd,Zn by 90.84%, 93.97% and 93.71%, respectively. Rotifer Brachionus plicatilis was used to conduct the assessment of wastewater toxicity. Following the application of Na 2 CS 3 , after 60 min the mortality of B. plicatilis was reduced from 90% to 25%. Engagement of Na 2 CS 3 under optimal conditions caused the precipitation of heavy metals from the polluted wastewater and significantly decreased wastewater toxicity. In summary, Na 2 CS 3 can be used as an effective heavy metal precipitating agent, especially for Cu, Cd and Zn.

Inflammatory diseases, whether caused by excessive stress on certain tissues/parts of the body or arising from infections accompanying autoimmune or secondary diseases, have become a problem, especially in the Western world today. Whether these are inflammations of visceral organs, joints, bones, or the like, they are always a physiological reaction of the body, which always tries to eradicate noxious agents and restore tissue homeostasis. Unfortunately, this often results in damage, often irreversible, to the affected tissues. Nevertheless, these inflammatory reactions of the body are the results of excessive stress, strain, and the generally unhealthy environment, in which the people of Western civilization live. The pathophysiology and pathobiochemistry of inflammatory/autoimmune processes are being studied in deep detail, and pharmaceutical companies are constantly developing new drugs that modulate/suppress inflammatory responses and endogenous pro-inflammatory agents. In addition to new specifically targeted drugs for a variety of pro-inflammatory agents, a strategy can be found for the use of older drugs, which are formulated into special nanodrug delivery systems with targeted distribution and often modified release. This contribution summarizes the current state of research and development of nanoformulated anti-inflammatory agents from both conventional drug classes and experimental drugs or dietary supplements used to alleviate inflammatory reactions.