Methoxychalcones as potential anticancer agents for colon cancer: Is membrane perturbing potency relevant?

Chalcones are naturally produced by many plants, and constitute precursors for the synthesis of flavons and flavanons. They were shown to possess antibacterial, antifungal, anti-cancer, and anti- inflammatory properties. The goal of the study was to assess the suitability of three synthetic methoxychalcones as potential anticancer agents. In a panel of colon cancer cell lines they were demonstrated to be cytotoxic, proapoptotic, causing cell cycle arrest, and increasing intracellular level of reactive oxygen species. Anticancer activity of the compounds was not diminished in the presence of stool extract containing microbial enzymes that could change the structure of chalcones. Moreover, methoxychalcones interacted strongly with model phosphatidylcholine membranes as detected by differential scanning calorimetry. Metohoxychalcones particularly affected the properties of lipid domains in giant unilamellar liposomes formed from raft-mimicking lipid composition. This may be of importance since many molecular targets for therapy of metastatic colon cancer are raft-associated receptors (e.g., receptor tyrosine kinases). The importance of membrane perturbing potency of methoxychalcones for their biological activity was additionally corroborated by the results obtained by molecular modelling.

Compensative Resistance to Erastin-Induced Ferroptosis in GPX4 Knock-Out Mutants in HCT116 Cell Lines.

Ferroptosis results from the accumulation of oxidized and damaged lipids which then leads to programmed cell death. This programmed process is iron-dependent, and as a fundamental biological process, plays a crucial role in tissue homeostasis. The ferroptosis molecular pathway depends on self-regulatory genes: GPX4; TFRC; ACSL4; FSP1; SLC7A11, and PROM2. Some of them were considered here as ferro-sensitive or ferro-resistance markers. We examined the impact of GPX4 gene knock-out, using the CRISPR/Cas-9 technique, on ferroptosis induction in the HCT116 colorectal cancer cell line. The results confirmed that cells lacking the GPX4 gene (GPX4 KO) should be more susceptible to ferroptosis after erastin treatment. However, the decrease in cell viability was not as significant as we initially assumed. Based on the lipid peroxidation markers profile and RT-qPCR gene expression analysis, we revealed the activation of an alternative antioxidant system supporting GPX4 KO cells, mostly for cellular ferroptotic death avoidance. Increased expression of FSP1 and PRDX1 genes in knock-out mutants was associated with their function-recognized here as ferroptosis suppressors. For such reasons, studies on the role of GPX4 and other crucial genes from the ferroptotic pathway should be explored. Despite promising prospects, the utilization of ferroptosis mechanisms in cancer therapy remains at the stage of experimental and in vitro preclinical studies.

Lactate exacerbates lung damage induced by nanomicroplastic through the gut microbiota-HIF1a/PTBP1 pathway.

Exposure to nanomicroplastics (nano-MPs) can induce lung damage. The gut microbiota is a critical modulator of the gut-lung axis. However, the mechanisms underlying these interactions have not been elucidated. This study explored the role of lactate, a key metabolite of the microbiota, in the development of lung damage induced by nano-MPs (LDMP). After 28 days of exposure to nano-MPs (50-100 nm), mice mainly exhibited damage to the lungs and intestinal mucosa and dysbiosis of the gut microbiota. Lactate accumulation was observed in the lungs, intestines and serum and was strongly associated with the imbalance in lactic acid bacteria in the gut. Furthermore, no lactate accumulation was observed in germ-free mice, while the depletion of the gut microbiota using a cocktail of antibiotics produced similar results, suggesting that lactate accumulation in the lungs may have been due to changes in the gut microbiota components. Mechanistically, elevated lactate triggers activation of the HIF1a/PTBP1 pathway, exacerbating nano-MP-induced lung damage through modulation of the epithelial-mesenchymal transition (EMT). Conversely, mice with conditional knockout of Ptbp1 in the lungs (Ptbp1flfl) and PTBP1-knockout (PTBP1-KO) human bronchial epithelial (HBE) cells showed reversal of the effects of lactate through modulation of the HIF1a/PTBP1 signaling pathway. These findings indicate that lactate is a potential target for preventing and treating LDMP.

Modulating pro-adhesive nature of metallic surfaces through a polypeptide coupling via diazonium chemistry.

The design of biomaterials able to facilitate cell adhesion is critical in the field of tissue engineering. Precise control of surface chemistry at the material/tissue interface plays a major role in enhancing the interactions between a biomaterial and living cells. Bio-integration is particularly important in case of various electrotherapies, since a close contact between tissue and electrode's surface facilitates treatment. A promising approach towards surface biofunctionalization involves the electrografting of diazonium salts followed by the modification of organic layer with pro-adhesive polypeptides. This study focuses on the modification of platinum electrodes with a 4-nitrobenzenediazonium layer, which is then converted to the aminobenzene moiety. The electrodes are further biofunctionalized with polypeptides (polylysine and polylysine/laminin) to enhance cell adhesion. This study also explores the differences between physical and chemical coupling of selected polypeptides to modulate pro-adhesive nature of Pt electrodes with respect to human neuroblastoma SH-SY5Y cells and U87 astrocytes. Our results demonstrate the significant enhancement in cell adhesion for biofunctionalized electrodes, with more amplified adhesion noted for covalently coupled polypeptides. The implications of this research are crucial for the development of more effective and functional biomaterials, particularly biomedical electrodes, which have the potential to advance the field of bioelectronics and improve patients' outcomes.

Polyurethane-Based Nanocomposites for Regenerative Therapies of Cancer Skin Surgery with Low Inflammatory Potential to Healthy Fibroblasts and Keratinocytes In Vitro.

Nanocomposites based on thermoplastic polyurethanes (TPUs) filled with halloysite nanotubes (HNTs) were studied for their physicochemical and biological properties. Nanocomposites containing halloysite nanotube filler contents of 1 and 2% (E+1 and E+2), respectively, were obtained by extrusion. The newly formed E+1 and E+2 nanomaterials exhibited better flexibility and similar thermal properties compared to neat polyurethane. The use of atomic force microscopy (AFM) and differential scanning calorimetry (DSC) thermogram analysis showed that the distribution of halloysite nanotubes in the polymer matrix is more evenly dispersed in the E+1 nanomaterial, where the grains in the E+2 nanomaterial have a greater tendency to form agglomerates. Mechanical tests have shown that nanocomposites with the addition of HNT are characterized by a higher stress at break and elongation at break compared to neat TPU. The results of cytotoxicity tests suggest that the nanocomposite materials express lower toxicity to normal HaCaT and NHDF than to cancer Me45 cells. Further studies showed that the tested materials induced the expression of proinflammatory interleukins IL6 and IL8 in normal cells, but their overexpression in the cancer cell line resulted in cytostatic effects and proliferation reduction. Such a conclusion suggests the possible application of tested materials for regenerative therapies in cancer surgeries.

Synthesis and in vitro cytotoxic activity of dye-linker-macrocycle conjugates with variable linker length and components.

The study investigated the structure-activity relationship of newly synthesized dye-linker-macrocycle (DLM) conjugates and the effect of each component on various biological properties, including cytotoxicity, cellular uptake, intracellular localization, interaction with DNA and photodynamic effects. The conjugates were synthesized by combining 1,8-naphthalimide and thioxanthone dyes with 1,4,7,10-tetraazacyclododecane (cyclen) and 1-aza-12-crown-4 (1A12C4) using alkyl linkers of different lengths. The results revealed significant differences in biological activity among the various series of conjugates. Particularly, 1A12C4 conjugates exhibited notably higher cytotoxicity compared to cyclen conjugates. Conjugation with 1A12C4 proved to be an effective strategy for increasing cellular uptake and cytotoxicity of small-molecule conjugates. In addition, the results highlighted the critical role of linker length in modulating the biological activity of DLM conjugates. It became clear that the choice of each component (dye, macrocycle and linker) could significantly alter the biological activity of the conjugates.

P53-response circRNA_0006420 aggravates lung cancer radiotherapy resistance by promoting formation of HUR/PTBP1 complex.

BACKGROUND: p53 wild-type lung cancer cells can develop radiation resistance. Circular RNA (circRNA) consists of a family of transcripts with exclusive structures. circRNA is critical in tumorigenesis and is a potential biomarker or therapeutic target. It is uncertain how circRNA expression and functions are regulated post-radiation in p53 wild-type cancer cells. METHODS: A549 or H1299 cells were divided into p53-wt and p53-KO groups by CRISPR/Cas9; both groups were subjected to 4 Gy ionizing radiation (IR: p53-wt-IR and p53-KO-IR). RNA-seq, CCK8, cell cycle, and other functional and mechanism experiments were performed in vivo. p53 gene knockout mice were generated to test the cell results in vitro. RESULTS: circRNAs were found in differential groups. circRNA_0006420 (IRSense) was upregulated in p53-wt cells but had the same expression level as p53-KO cells after radiation, indicating that p53 silencing prevents its upregulation after IR. In the presence of p53, upregulated IRSense post-radiation induces G2/M arrest by regulating DNA damage repair (DDR) pathway-related proteins. Meanwhile, upregulated IRSense post-radiation aggravates the radiation-induced epithelial-mesenchymal transition (EMT). Interestingly, in the presence of p53, it promotes IRSense/HUR/PTBP1 complex formation resulting in the promotion of the radiation-induced EMT. Moreover, c-Jun regulates the upregulation of p53 transcription after radiation treatment. For these lung cancer cells with p53, upregulated IRSense aggravates lung cancer cell proliferation and increases radiation resistance by interacting with HUR (ElAV-like protein 1) and PTBP1 (polypyrimidine tract-binding protein 1) in the nucleus. CONCLUSIONS: Lung cancer cells retaining p53 may upregulate circRNA_0006420 (IRSense) expression post radiation to form an IRSense/HUR/PTBP1 complex leading to radiotherapy resistance. This study furthers our understanding of the roles of circRNA in regulating the effect of radiotherapy and provides novel therapeutic avenues for effective clinical lung cancer therapies.

Nanoparticles-induced potential toxicity on human health: Applications, toxicity mechanisms, and evaluation models.

Nanoparticles (NPs) have become one of the most popular objects of scientific study during the past decades. However, despite wealth of study reports, still there is a gap, particularly in health toxicology studies, underlying mechanisms, and related evaluation models to deeply understanding the NPs risk effects. In this review, we first present a comprehensive landscape of the applications of NPs on health, especially addressing the role of NPs in medical diagnosis, therapy. Then, the toxicity of NPs on health systems is introduced. We describe in detail the effects of NPs on various systems, including respiratory, nervous, endocrine, immune, and reproductive systems, and the carcinogenicity of NPs. Furthermore, we unravels the underlying mechanisms of NPs including ROS accumulation, mitochondrial damage, inflammatory reaction, apoptosis, DNA damage, cell cycle, and epigenetic regulation. In addition, the classical study models such as cell lines and mice and the emerging models such as 3D organoids used for evaluating the toxicity or scientific study are both introduced. Overall, this review presents a critical summary and evaluation of the state of understanding of NPs, giving readers more better understanding of the NPs toxicology to remedy key gaps in knowledge and techniques.

Surface grafting of poly-L-lysine via diazonium chemistry to enhance cell adhesion to biomedical electrodes.

The ability to study and regulate cell behavior at a biomaterial interface requires a strict control over its surface chemistry. Significance of studying cell adhesion in vitro and in vivo has become increasingly important, particularly in the field of tissue engineering and regenerative medicine. A promising surface modification route assumes using organic layers prepared by the method of electrografting of diazonium salts and their further functionalization with biologically active molecules as cell adhesion promoters. This work reports the modification of platinum electrodes with selected diazonium salts and poly-L-lysine to increase the number of sites available for cell adhesion. As-modified electrodes were characterized in terms of their chemical and morphological properties, as well as wettability. In order to monitor the process of cell attachment, biofunctionalized electrodes were used as substrates for culturing human neuroblastoma SH-SY5Y cells. The experiments revealed that cell adhesion is favored on the surface of diazonium-modified and poly-L-lysine coated electrodes, indicating proposed modification route as a valuable strategy enhancing the integration between bioelectronic devices and neural cells.

14-Substituted Diquinothiazines as a New Group of Anticancer Agents.

A series of novel double-angularly condensed diquinothiazines with aminoalkyl, amidoalkyl, sulfonamidoalkyl, and substituted phenyl groups was designed, synthesized, and evaluated for their anticancer activity against four selected human tumor cell lines (HTC116, SH-SY5Y, A549, and H1299). The cytotoxicity of the novel diquinothiazines was investigated against BEAS-2B cells. The activities of the compounds were compared to etoposide. Among them, compounds with aminoalkyl and phenyl groups showed excellent broad-spectrum anticancer activity. The most active 14-(methylthiophenyl)diquinothiazine, 3c, showed low cytotoxicity against BEAS-2B cells and high activity against tumor cell lines HTC116, SH-SY5Y, A549, and H1299, with IC50 values of 2.3 µM, 2.7 µM, 17.2 µM, and 2.7 µM, respectively (etopiside 8.6 µM, 3.9 µM, 44.8 µM, and 0.6, respectively). Live long-term microscopic observations of cell survival using the starting molecule M0 were also performed. Flow cytometry showed the proapoptotic effects of the studied diquinothiazines. Inhibition of the cell cycle in the S phase was observed, which is associated with damage to nucleic acids and connected to DNA replication arrest.

Glycoconjugates of Mucochloric Acid-Synthesis and Biological Activity.

The pharmacological effects of the presence of a sugar moiety, 1,2,3-triazole ring and silyl groups in the structure of biologically active compounds have been extensively studied in drug design and medicinal chemistry. These components can be useful tools to tailoring the bioavailability of target molecules. Herein we present the study on the impact of the sugar substituent structure and triisopropylsilyl group presence on the anticancer activity of mucochloric acid (MCA) derivatives containing the furan-2(5H)-one or 2H-pyrrol-2-one core. The obtained results clearly indicated that tested compounds caused a significant decrease in cell viability of HCT116 and MCF-7 cell lines. MCF-7 cells indicate serious resistance toward investigated compounds in comparison with HCT116 cell line, it suggests that estrogen-dependent breast cancer cells are significantly less sensitive to the tested derivatives. Depending on the structure of the sugar, the type and site of connection with the furanone or 2H-pyrrol-2-one derivative and the presence of the silyl group, the selectivity of the compound towards cancer cells can be controlled. The obtained results may have an impact on the design of new furanone-based anticancer compounds.

Toxicity evaluation of choline ionic liquid-based nanocarriers of pharmaceutical agents for lung treatment.

In vitro cytotoxicity evaluation of linear copolymer (LC) containing choline ionic liquid units and its conjugates with an antibacterial drug in anionic form, that is, p-aminosalicylate (LC_PAS), clavulanate (LC_CLV), or piperacillin (LC_PIP) was carried out. These systems were tested against normal: human bronchial epithelial cells (BEAS-2B), and cancers: adenocarcinoma human alveolar basal epithelial cells (A549), and human non-small cell lung carcinoma cell line (H1299). Cells viability, after linear copolymer LC and their conjugates addition for 72 h, was measured at concentration range of 3.125-100 µg/mL. The MTT test allowed the designation of IC50 index, which was higher for BEAS-2B, and significantly lower in the case of cancer cell lines. The cytometric analyzes, that is, Annexin-V FITC apoptosis assay and cell cycle analysis as well as gene expression measurements for interleukins IL6 and IL8 were carried out, and showed pro-inflammatory activity of tested compounds toward cancer cells, while it was not observed against normal cell line.

Comparison of the degradation mechanisms of diclofenac in the presence of iron octacarboxyphthalocyanine and myeloperoxidase.

The degradation process of diclofenac (DCF) by hematoprotein myeloperoxidase (MPO) and iron octacarboxyphthalocyanine (FePcOC) in the presence of hydrogen peroxide was compared. During the oxidation of diclofenac, in the presence of iron octacarboxyphthalocyanine (FePcOC) and hydroxyl radicals (HO•) (from H2O2), an intermediate product (dimer with an m/z value of 587) with the characteristic yellow colouration and an intense band at λmax = 451 nm is formed. Iron octacarboxyphthalocyanine oxidises in the presence of hydrogen peroxide, following the first-order reaction kinetics for FePcOC and H2O2. The concentration of diclofenac does not affect the initial reaction rate. For comparison, the oxidation of DCF in the presence of myeloperoxidase and hydrogen peroxide also provided yellow-coloured solutions with an absorption maximum at λmax = 451 nm. However, LC-MS/MS analysis indicates the presence of at least seven main products of the diclofenac oxidation process in the final reaction mixture, including two dimers with the ion mass [M-H]¯ = 587.01. The mechanism of the diclofenac degradation with hematoprotein myeloperoxidase is more complex than with iron octacarboxyphthalocyanine. Furthermore, the biological activity of diclofenac and DCF dimer (iron octacarboxyphthalocyanine and hydroxyl radicals degradation product) was tested. In this case, the long-term assayed in vitro against E. coli, colorectal HCT116 and melanoma Me45 cancer cells were performed.

Glycoconjugation of Quinoline Derivatives Using the C-6 Position in Sugars as a Strategy for Improving the Selectivity and Cytotoxicity of Functionalized Compounds.

Based on the Warburg effect and the increased demand for glucose by tumor cells, a targeted drug delivery strategy was developed. A series of new glycoconjugates with increased ability to interact with GLUT transporters, responsible for the transport of sugars to cancer cells, were synthesized. Glycoconjugation was performed using the C-6 position in the sugar unit, as the least involved in the formation of hydrogen bonds with various aminoacids residues of the transporter. The carbohydrate moiety was connected with the 8-hydroxyquinoline scaffold via a 1,2,3-triazole linker. For the obtained compounds, several in vitro biological tests were performed using HCT-116 and MCF-7 cancer cells as well as NHDF-Neo healthy cells. The highest cytotoxicity of both cancer cell lines in the MTT test was noted for glycoconjugates in which the triazole-quinoline was attached through the triazole nitrogen atom to the d-glucose unit directly to the carbon at the C-6 position. These compounds were more selective than the analogous glycoconjugates formed by the C-1 anomeric position of d-glucose. Experiments with an EDG inhibitor have shown that GLUTs can be involved in the transport of glycoconjugates. The results of apoptosis and cell cycle analyses by flow cytometry confirmed that the new type of glycoconjugates shows pro-apoptotic properties, without significantly affecting changes in the distribution of the cell cycle. Moreover, glycoconjugates were able to decrease the clonogenic potential of cancer cells, inhibit the migration capacity of cells and intercalate with DNA.

Hepatocellular cancer cell lines, Hep-3B and Hep-G2 display the pleiotropic response to resveratrol and berberine.

PURPOSE: Human carcinoma cells with different p53 status exposed to a combination of bioactive substances, resveratrol and berberine, revealed different responses in cell viability via p53-dependant apoptosis pathway activation. MATERIALS AND METHODS: Using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, we investigated various and opposing effects in hepatocellular carcinoma cells, Hep-G2 and Hep-3B with different p53-status. RESULTS: Cells decreased in viability after treatment with dose-dependent concentrations of resveratrol and berberine. Hep-3B p53 mutants were more sensitive in comparison to the p53 wild type Hep-G2 cell line. A synergistic effect was observed after treatment of Hep-3B cells with a combination of resveratrol/berberine ratios in favor of resveratrol (2:1, 3:1). The results suggest that an effective concentration of berberine, in the presence of resveratrol, could be decreased even to 50% (half the IC50 for berberine) in cancer treatment. Combined treatment with berberine and resveratrol, at the investigated concentrations and fractions, significantly reduces the viability of wild type p53 Hep-G2 and null p53-mutant Hep-3B cells by 20% and 40%, respectively. CONCLUSIONS: Stronger toxic effects on viability and proliferation were observed in Hep-3B cells what is consistent with the assumptions that null p53-mutants activate apoptosis canonical pathway. In conclusion, p53 status in human hepatocellular cancer cell lines modulates responses to plant-derived therapies.

Tri- and Pentacyclic Azaphenothiazine as Pro-Apoptotic Agents in Lung Carcinoma with a Protective Potential to Healthy Cell Lines.

The phenothiazine derivatives, tricyclic 10H-3,6-diazaphenothiazine (DPT-1) and pentacyclic 7-(3'-dimethylaminopropyl)diquinothiazine (DPT-2), have recently been shown to exhibit promising anticancer activities in vitro. In this report, we demonstrated that DPT-1 and DPT-2 could be pro-apoptotic agents in lung carcinoma, the human lung carcinoma A549 and non-small lung carcinoma H1299, in the range of IC50 = 1.52-12.89 µM, with a protective potential to healthy cell lines BEAS-2B and NHDF. The compounds showed higher activity in the range of the tested concentrations and low cytotoxicity in relation to normal healthy cells than doxorubicin, used as the reference drug. The cytostatic potential of DPT-1 and DPT-2 was demonstrated with the use of MTT assay. Cell cycle analysis via flow cytometry using Annexin-V assay showed the pro-apoptotic and pro-necrotic role of the studied diazaphenothiazines in the cell cycle. DPT-1 and DPT-2 initiated a biological response in the investigated cancer models with a different mechanism and at a different rate. Based on these findings, it can be concluded that DPT-1 and DPT-2 have potential as chemotherapeutic agents.

The Use of Endo-Cellulase and Endo-Xylanase for the Extraction of Apple Pectins as Factors Modifying Their Anticancer Properties and Affecting Their Synergy with the Active Form of Irinotecan.

Pectin constitutes an essential component of dietary fiber. Modified pectins from various sources possess potent anticancer and immunomodulatory activities. In this study, two pectins isolated from apple pomace by Trichoderma enzyme treatment, PX (with endo-xylanase) and PCX (with both endo-cellulase and endo-xylanase), were studied in colon cancer cell lines (HCT 116, Caco-2, and HT-29). Both pectins reduced colon cancer cell viability, induced apoptosis, and increased intracellular amounts of reactive oxygen species. Additionally, synergy between pectin and an active form of irinotecan, SN-38, in all aspects mentioned above, was discovered. This drug is a common component of cytotoxic combinations recommended as treatment for colon cancer patients. PX and PCX demonstrated significant anti-inflammatory activity in lipopolysaccharide-stimulated cells. Interaction of apple pectins with galectin-3 and Toll-like Receptor 4 (TLR4) was suggested to be responsible for their anticancer and anti-inflammatory effect. Since PCX was more active than PX in almost all experiments, the role of the enzyme used to obtain the pectin for its biological activity was discussed. It was concluded that co-operation between both enzymes was needed to obtain the molecule of the most beneficial properties. The low molecular mass of PCX together with a high proportion of rhamnogalacturonan I (RG I) regions seemed to be crucial for its superior activity.

Shell-Sheddable Micelles Based on Poly(ethylene glycol)-hydrazone-poly[R,S]-3-hydroxybutyrate Copolymer Loaded with 8-Hydroxyquinoline Glycoconjugates as a Dual Tumor-Targeting Drug Delivery System.

The development of selective delivery of anticancer drugs into tumor tissues to avoid systemic toxicity is a crucial challenge in cancer therapy. In this context, we evaluated the efficacy of a combination of nanocarrier pH-sensitivity and glycoconjugation of encapsulated drugs, since both vectors take advantage of the tumor-specific Warburg effect. Herein, we synthesized biodegradable diblock copolymer, a poly(ethylene glycol)-hydrazone linkage-poly[R,S]-3-hydroxybutyrate, which could further self-assemble into micelles with a diameter of ~55 nm. The hydrazone bond was incorporated between two copolymer blocks under an acidic pH, causing the shell-shedding of micelles which results in the drug's release. The micelles were stable at pH 7.4, but decompose in acidic pH, as stated by DLS studies. The copolymer was used as a nanocarrier for 8-hydroxyquinoline glucose and galactose conjugates as well as doxorubicin, and exhibited pH-dependent drug release behavior. In vitro cytotoxicity, apoptosis, and life cycle assays studies of blank and drug-loaded micelles were performed on Normal Human Dermal Fibroblasts-Neonatal (NHDF-Neo), colon carcinoma (HCT-116), and breast cancer (MCF-7) for 24, 48, and 72 h. A lack of toxicity of blank micelles was demonstrated, whereas the glycoconjugates-loaded micelles revealed enhanced selectivity to inhibit the proliferation of cancer cells. The strategy of combining pH-responsive nanocarriers with glycoconjugation of the drug molecule provides an alternative to the modus operandi of designing multi-stimuli nanocarriers to increase the selectivity of anticancer therapy.

Bifunctional conducting polymer matrices with antibacterial and neuroprotective effects.

Current trends in the field of neural tissue engineering include the design of advanced biomaterials combining excellent electrochemical performance with versatile biological characteristics. The purpose of this work was to develop an antibacterial and neuroprotective coating based on a conducting polymer - poly(3,4-ethylenedioxypyrrole) (PEDOP), loaded with an antibiotic agent - tetracycline (Tc). Employing an electrochemical technique to immobilize Tc within a growing polymer matrix allowed to fabricate robust PEDOP/Tc coatings with a high charge storage capacity (63.65 ± 6.05 mC/cm2), drug release efficiency (629.4 µg/cm2 ± 62.7 µg/cm2), and low charge transfer resistance (2.4 ± 0.1 kΩ), able to deliver a stable electrical signal. PEDOP/Tc were found to exhibit strong antimicrobial effects against Gram-negative bacteria Escherichia coli, expressed through negligible adhesion, reduction in viability, and a characteristic elongation of bacterial cells. Cytocompatibility and neuroprotective effects were evaluated using a rat neuroblastoma B35 cell line, and were analyzed using MTT, cell cycle, and Annexin-V apoptosis assays. The presence of Tc was found to enhance neural cell viability and neurite outgrowth. The results confirmed that PEDOP/Tc can serve as an efficient neural electrode coating able to enhance charge transfer, as well as to exhibit bifunctional biological characteristics, different for eukaryotic and prokaryotic cells.

Synthesis and Preliminary Anticancer Activity Assessment of N-Glycosides of 2-Amino-1,3,4-thiadiazoles.

The addition of 2-amino-1,3,4-thiadiazole derivatives with parallel iodination of differently protected glycals has been achieved using a double molar excess of molecular iodine under mild conditions. The corresponding thiadiazole derivatives of N-glycosides were obtained in good yields and anomeric selectivity. The usage of iodine as a catalyst makes this method easy, inexpensive, and successfully useable in reactions with sugars. Thiadiazole derivatives were tested in a panel of three tumor cell lines, MCF-7, HCT116, and HeLa. These compounds initiated biological response in investigated tumor models in a different rate. The MCF-7 is resistant to the tested compounds, and the cytometry assay indicated low increase in cell numbers in the sub- G1 phase. The most sensitive are HCT-116 and HeLa cells. The thiadiazole derivatives have a pro-apoptotic effect on HCT-116 cells. In the case of the HeLa cells, an increase in the number of cells in the sub-G1- phase and the induction of apoptosis was observed.