Fluorine materials scavenge excess carbon dioxide and promote Escherichia coli growth.

Fluorinated solvents have been used as oxygen carriers in closed microbial cultures to sustain aerobic conditions. However, the growth-promoting effects of fluorinated solvents remain unclear. Therefore, this study aimed to elucidate the mechanism by which fluorinated solvents promote microbial growth and to explore alternative materials that can be easily isolated after culture. Escherichia coli and HFE-7200, a fluorinated solvent, were used to explore factors other than oxygen released by fluorinated solvents that promote microbial growth. E. coli growth was promoted in gas-permeable cultures, and HFE-7200 alleviated medium acidification. Gas chromatography confirmed that HFE-7200 functioned as a scavenger of carbon dioxide produced by E. coli metabolism. Because fluorinated solvents can dissolve various gases, they could scavenge metabolically produced toxic gases from microbial cultures. Furthermore, using polytetrafluoroethylene, a solid fluorine material, results in enhanced bacterial growth. Such solid materials can be easily isolated and reused for microbial culture, suggesting their potential as valuable technologies in food production and biotechnology.

Antibacterial Activity of Boron Compounds Against Biofilm-Forming Pathogens.

This study aimed to evaluate the antibacterial activity of nine boron derivatives against biofilm-forming pathogenic bacteria. The effect of boron derivatives (CMB, calcium metaborate; SMTB, sodium metaborate tetrahydrate; ZB, zinc borate; STFB, sodium tetra fluorine borate; STB, sodium tetraborate; PTFB, potassium tetra fluor borate; APTB, ammonium pentabo-rate tetrahydrate; SPM, sodium perborate monohydrate; Borax, ATFB, ammonium tetra fluorine borate) on bacteria isolated from blood culture was determined by the minimum inhibitory concentration (MIC) method. Then, biofilm formation potentials on microplates, tubes, and Congo red agar were examined. The cytotoxicity of boron derivatives was determined by using WST-1-based methods. The interaction between the biofilm-forming bacteria, fibroblast cells, and boron derivatives was determined with the infection model. We found that the sodium metaborate tetrahydrate molecule was effective against all pathogens. According to the optical density values detected at 630 nm in microplates, meticillin-resistant Staphylococcus aureus was observed to have the most substantial biofilm ability at 0.257 nm. As a result of cytotoxicity studies, it has been determined that a 1 µg/L concentration of boron derivatives is not toxic to fibroblast L929 cells. In cell culture experiments, these boron derivatives have very serious inhibitory activity against biofilm-forming pathogens in a short treatment period, such as 2-4 h. Furthermore, using these molecules on inanimate surfaces affected by biofilms would be appropriate instead of living cells.

Insecticidal and Repellent Properties of Rapid-Acting Fluorine-Containing Compounds against Aedes aegypti Mosquitoes.

The development of safe and potent insecticides remains an integral part of a multifaceted strategy to effectively control human-disease-transmitting insect vectors. Incorporating fluorine can dramatically alter the physiochemical properties and bioavailability of insecticides. For example, 1,1,1-trichloro-2,2-bis(4-fluorophenyl)ethane (DFDT)─a difluoro congener of trichloro-2,2-bis(4-chlorophenyl)ethane (DDT)─was demonstrated previously to be 10-fold less toxic to mosquitoes than DDT in terms of LD50 values, but it exhibited a 4-fold faster knockdown. Described herein is the discovery of fluorine-containing 1-aryl-2,2,2-trichloro-ethan-1-ols (FTEs, for fluorophenyl-trichloromethyl-ethanols). FTEs, particularly per-fluorophenyl-trichloromethyl-ethanol (PFTE), exhibited rapid knockdown not only against Drosophila melanogaster but also against susceptible and resistant Aedes aegypti mosquitoes, major vectors of Dengue, Zika, yellow fever, and Chikungunya viruses. The R enantiomer of any chiral FTE, synthesized enantioselectively, exhibited faster knockdown than its corresponding S enantiomer. PFTE does not prolong the opening of mosquito sodium channels that are characteristic of the action of DDT and pyrethroid insecticides. In addition, pyrethroid/DDT-resistant Ae. aegypti strains having enhanced P450-mediated detoxification and/or carrying sodium channel mutations that confer knockdown resistance were not cross-resistant to PFTE. These results indicate a mechanism of PFTE insecticidal action distinct from that of pyrethroids or DDT. Furthermore, PFTE elicited spatial repellency at concentrations as low as 10 ppm in a hand-in-cage assay. PFTE and MFTE were found to possess low mammalian toxicity. These results suggest the substantial potential of FTEs as a new class of compounds for controlling insect vectors, including pyrethroid/DDT-resistant mosquitoes. Further investigations of FTE insecticidal and repellency mechanisms could provide important insights into how incorporation of fluorine influences the rapid lethality and mosquito sensing.

Low dosage fluorine ameliorates the bioaccumulation, hepatorenal dysfunction and oxidative stress, and gut microbiota perturbation of cadmium in rats.

Many "hot spot" geographic areas around the world with soils and crops co-polluted with cadmium (Cd) and fluorine (F), two of the most representative pollutants in the environment. However, it still exists argumentative on the dose-effect relationship between F and Cd so far. To explore this, a rat model was established to evaluate the effects of F on Cd-mediated bioaccumulation, hepatorenal dysfunction and oxidative stress, and the disorder of intestinal microbiota as well. 30 healthy rats were randomly assigned to Control group (C group), Cd 1 mg/kg (Cd group), Cd 1 mg/kg and F 15 mg/kg (L group), Cd 1 mg/kg and F 45 mg/kg (M group), and Cd 1 mg/kg and F 75 mg/kg (H group) for 12 weeks by gavage. Our results showed that Cd exposure could accumulate in organs, cause hepatorenal function damage and oxidative stress, and disorder of gut microflora. However, different dosages of F showed various effects on Cd-induced damages in liver, kidney, and intestine, and only the low supplement of F showed a consistent trend. After low supplement of F, Cd levels were declined by 31.29% for liver, 18.31% for kidney, and 2.89% for colon, respectively. The serum aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine (Cr), and N-acetyl-ß-glucosaminidase (NAG) were significantly reduced (p < 0.01); The activity of superoxide dismutase (SOD) was elevated and mRNA expression level of NAD(P)H quinone oxidoreductase 1 (NQO1) was decreased in the liver and kidney (p < 0.05). Moreover, low F dosage up-regulated the abundance of Lactobacillus from 15.56% to 28.73% and the 6.23% of F/B ratio was declined to 3.70%. Collectively, this highlights that low dosage of F might be a potential strategy to ameliorate the hazardous effects by Cd-exposed in the environment.

The Effects of Vitamin D Application on NaF-Induced Cytotoxicity in Osteoblast Cells (hFOB 1.19).

This study was planned to evaluate the effect of vitamin D administration on cytotoxicity due to fluoride exposure in vitro. NaF (IC50) and vitamin D (proliferative) were applied to human osteoblast (hFOB 1.19) cells. The major genes of apoptotic, autophagic, and necrotic pathways were determined by RT-PCR. 2-∆∆Ct formulation was used for expression analysis. In the NaF group, caspase 3, Bax, Bad, Bak, Bclx, Atg3, Atg5, Atg6, pG2, LC3-I, LC3-II, RIP1, and RIP3 genes were increased (2.6-15 times). It was observed that the expressions of these genes approached the control when vitamin D was given together with NaF. The Bcl2 gene increased significantly (sixfold) with the effect of NaF, and was down-regulated to some extent with additional vitamin D administration, but still more than in the control. As a result, it was determined that apoptotic, necrotic, and autophagic pathways were activated as the molecular basis of the damage in the bone tissue, which was most affected by fluorine, and these genes were down-regulated and approached the control group with the addition of vitamin D. It was concluded that this is an important data to explain the molecular basis of the protective and therapeutic effect of vitamin D against fluorine toxicity.

Fluorine labelling of therapeutic human tolerogenic dendritic cells for 19F-magnetic resonance imaging.

Tolerogenic dendritic cell (tolDC) therapies aim to restore self-tolerance in patients suffering from autoimmune diseases. Phase 1 clinical trials with tolDC have shown the feasibility and safety of this approach, but have also highlighted a lack of understanding of their distribution in vivo. Fluorine-19 magnetic resonance imaging (19F-MRI) promises an attractive cell tracking method because it allows for detection of 19F-labelled cells in a non-invasive and longitudinal manner. Here, we tested the suitability of nanoparticles containing 19F (19F-NP) for labelling of therapeutic human tolDC for detection by 19F-MRI. We found that tolDC readily endocytosed 19F-NP with acceptable effects on cell viability and yield. The MRI signal-to-noise ratios obtained are more than sufficient for detection of the administered tolDC dose (10 million cells) at the injection site in vivo, depending on the tissue depth and the rate of cell dispersal. Importantly, 19F-NP labelling did not revert tolDC into immunogenic DC, as confirmed by their low expression of typical mature DC surface markers (CD83, CD86), low secretion of pro-inflammatory IL-12p70, and low capacity to induce IFN-γ in allogeneic CD4+ T cells. In addition, the capacity of tolDC to secrete anti-inflammatory IL-10 was not diminished by 19F-NP labelling. We conclude that 19F-NP is a suitable imaging agent for tolDC. With currently available technologies, this imaging approach does not yet approach the sensitivity required to detect small numbers of migrating cells, but could have important utility for determining the accuracy of injecting tolDC into the desired target tissue and their efflux rate.

Constructing fluorine-doped Zr-MOF films on titanium for antibacteria, anti-inflammation, and osteogenesis.

Implant infection, undesirable inflammation, and poor osseointegration are the primary reasons for implant failure, so it is pivotal to endow bone implants with antibacterial, anti-inflammatory, and osteogenic properties. Here, a multifunctional fluorine-doped zirconium-metal organic framework (Zr-MOF) film was constructed on the titanium to modify its biological performances. The fumaric acid, a common antioxidant, was selected as the ligand of Zr-MOF, and the hydrofluoric acid was used as the modulator to control the growth of Zr-MOF film. The obtained fluorine-doped Zr-MOF film possessed good biocompatibility and osteogenic ability, and it showed good antibacterial effects against both gram-positive S. aureus and gram-negative E. coli due to the release of fluoride ions. In addition, the doping of fluorine could reduce the stability of Zr-MOF by substituting fumaric acid, and stimulating the releases of fumaric acid. Furthermore, the fumaric acid released from Zr-MOF could down-regulate the expression of pro-inflammatory genes (NF-κB and IL-6), but up-regulate the expression of anti-inflammatory gene of IL-4 of macrophage, showing good anti-inflammatory ability. This study provided a reference for the modulation synthesis of MOF film, and proposed a promising strategy of designing Zr-MOF film to endow bone implants with antibacterial, anti-inflammatory, and osteogenic abilities.

Overcoming undesirable hERG affinity by incorporating fluorine atoms: A case of MAO-B inhibitors derived from 1 H-pyrrolo-[3,2-c]quinolines.

The incorporation of the fluorine motif is a strategy widely applied in drug design for modulating the activity, physicochemical parameters, and metabolic stability of chemical compounds. In this study, we attempted to reduce the affinity for ether-à-go-go-related gene (hERG) channel by introducing fluorine atoms in a group of 1H-pyrrolo[3,2-c]quinolines that are capable of inhibiting monoamine oxidase type B (MAO-B). A series of structural modifications guided by in vitro evaluation of MAO-B inhibition and antitargeting for hERG channels were performed, which led to the identification of 1-(3-chlorobenzyl)-4-(4,4-difluoropiperidin-1-yl)-1H-pyrrolo[3,2-c]quinoline (26). Compound 26 acted as a reversible MAO-B inhibitor exhibiting selectivity over 45 targets, enzymes, transporters, and ion channels, and showed potent glioprotective properties in cultured astrocytes. In addition, the compound demonstrated good metabolic stability in rat liver microsomes assay, a favorable safety profile, and brain permeability. It also displayed procognitive effects in the novel object recognition test in rats and antidepressant-like activity in forced swim test in mice. The findings of the study suggest that reversible MAO-B inhibitors can have potential therapeutic applications in Alzheimer's disease.

Potentiation of antibiotic activity, and efflux pumps inhibition by (2E)-1-(4-aminophenyl)-3-(4-fluorophenyl)prop-2-en-1-one.

In recent years, bacterial resistance to traditional drugs has increased, and the need to find new effective antibiotics to treat infections caused by multidrug-resistant bacteria has consequently become more important. The current study aimed to evaluate the potentiation of antibiotic activity and efflux pumps inhibition by (2E)-1-(4-aminophenyl)-3-(4-fluorophenyl)prop-2-en-1-one (PA-Fluorine) against the standard and resistant bacterial strains of Staphylococcus aureus and Escherichia coli. The association between PA-Fluorine and ampicillin reduced the minimum inhibitory concentration (MIC), showing a synergistic effect against S. aureus. For E. coli, PA-Fluorine did not show any significant results when associated with ampicillin. Ciprofloxacin and chlorpromazine showed synergy with PA-Fluorine on the two studied strains. An efflux pump mechanism was involved in the mechanism of action of chlorpromazine, norfloxacin, and ethidium bromide. PA-Fluorine synergistically modulated norfloxacin and bromide. It was thus concluded that PA-Fluorine has the potential to enhance antibacterial activity when combined with antibiotics. Molecular docking studies showed the effect of intermolecular interactions of PA-Fluorine on the NorA and MepA efflux pumps. Physicochemical and pharmacokinetic properties were also obtained by ADMET studies for this chalcone, which presents be a strong candidate as an efflux pump inhibitor.

Research Advancements on Fluorinated and Non-Fluorinated 4- Phenyl(thio)ureido-Substituted 2,2-Dimethylchromans Acting as Inhibitors of Insulin Release and Smooth Muscle Relaxants.

AIMS: The present study aimed at characterizing the impact of the presence or absence of fluorine atoms on the phenyl and benzopyran rings of 4-phenyl(thio)ureido-substituted 2,2- dimethylchromans on their ability to inhibit insulin release from pancreatic ß-cells or to relax vascular smooth muscle cells. METHODS: Most compounds were found to inhibit insulin secretion and to provoke a marked myorelaxant activity. RESULTS: The lack of a fluorine or chlorine atom at the 6-position of the 2,2-dimethylchroman core structure reduced the inhibitory activity on the pancreatic endocrine tissue. One of the most active compounds on both tissues, compound 11h (BPDZ 678), was selected for further pharmacological investigations. CONCLUSION: The biological data suggested that 11h mainly expressed the profile of a KATP channel opener on pancreatic ß-cells, although a calcium entry blockade effect was also observed. On vascular smooth muscle cells, 11h behaved as a calcium entry blocker.

Integration of Au Nanosheets and GdOF:Yb,Er for NIR-I and NIR-II Light-Activated Synergistic Theranostics.

The local hyperthermia (>41 °C) effect of photothermal therapy (PTT) is significantly limited by the efficiency of PTT agents to convert laser energy to heat, and such oncotherapy, similar to conventional chemotherapy, invariably encounters the challenge of nonspecific application. Undue reliance on oxygen sources still poses particular difficulties in photodynamic therapy (PDT) for deep-level clinical applications. Considering these therapeutic issues, in this study, we constructed a versatile but unique nanosystem by encapsulating Au nanosheets in codoped gadolinium oxyfluoride (GdOF):Yb,Er spheres, followed by decoration of a chemotherapeutic drug (doxorubicin), photosensitizer (rose Bengal, RB), and targeted agent (folic acid). This allowed the incorporation of cancer treatment and real-time curative efficacy monitoring into one single theranostic nanoplatform. Benefiting from the dual contribution of the strong absorptions in the NIR-I and NIR-II regions, relevant photothermal-conversion efficiency (η) values pertaining to that final product were 39.2% at 1064 nm irradiation and 35.7% at 980 nm illumination. The fluorescence resonance energy transfer that occurred in the up-converted GdOF:Yb,Er to RB contributed to the high PDT efficacy. Combined with a micromeric acid-responsive drug release in a targeted tumor microenvironment, high-performance synergistic therapy was realized. In addition, up-conversion fluorescence imaging and computed tomography imaging accompanied by multimodal magnetic resonance imaging were simultaneously achieved owing to the doped lanthanide ions and the encapsulated Au nanosheets. Our designed oncotherapy nanosystem provides an alternative strategy to acquire ideal theranostic effects.

Fluorine Modifications Contribute to Potent Antiviral Activity against Highly Drug-Resistant HIV-1 and Favorable Blood-Brain Barrier Penetration Property of Novel Central Nervous System-Targeting HIV-1 Protease Inhibitors In Vitro.

To date, there are no specific treatment regimens for HIV-1-related central nervous system (CNS) complications, such as HIV-1-associated neurocognitive disorders (HAND). Here, we report that two newly generated CNS-targeting HIV-1 protease (PR) inhibitors (PIs), GRL-08513 and GRL-08613, which have a P1-3,5-bis-fluorophenyl or P1-para-monofluorophenyl ring and P2-tetrahydropyrano-tetrahydrofuran (Tp-THF) with a sulfonamide isostere, are potent against wild-type HIV-1 strains and multiple clinically isolated HIV-1 strains (50% effective concentration [EC50]: 0.0001 to ∼0.0032 µM). As assessed with HIV-1 variants that had been selected in vitro to propagate at a 5 µM concentration of each HIV-1 PI (atazanavir, lopinavir, or amprenavir), GRL-08513 and GRL-08613 efficiently inhibited the replication of these highly PI-resistant variants (EC50: 0.003 to ∼0.006 µM). GRL-08513 and GRL-08613 also maintained their antiviral activities against HIV-2ROD as well as severely multidrug-resistant clinical HIV-1 variants. Additionally, when we assessed with the in vitro blood-brain barrier (BBB) reconstruction system, GRL-08513 and GRL-08613 showed the most promising properties of CNS penetration among the evaluated compounds, including the majority of FDA-approved combination antiretroviral therapy (cART) drugs. In the crystallographic analysis of compound-PR complexes, it was demonstrated that the Tp-THF rings at the P2 moiety of GRL-08513 and GRL-08613 form robust hydrogen bond interactions with the active site of HIV-1 PR. Furthermore, both the P1-3,5-bis-fluorophenyl- and P1-para-monofluorophenyl rings sustain greater contact surfaces and form stronger van der Waals interactions with PR than is the case with darunavir-PR complex. Taken together, these results strongly suggest that GRL-08513 and GRL-08613 have favorable features for patients infected with wild-type/multidrug-resistant HIV-1 strains and might serve as candidates for a preventive and/or therapeutic agent for HAND and other CNS complications.

Design, synthesis and SAR study of Fluorine-containing 3rd-generation taxoids.

It has been shown that the incorporation of fluorine or organofluorine groups into pharmaceutical and agricultural drugs often induces desirable pharmacological properties through unique protein-drug interactions involving fluorine. We have reported separately remarkable effects of the 2,2-difluorovinyl (DFV) group at the C3' position, as well as those of the CF3O and CHF2O groups at the 3-position of the C2-benzoyl moiety of the 2nd- and 3rd-generation taxoids on their potency and pharmacological properties. Thus, it was very natural for us to investigate the combination of these two modifications in the 3rd-generation taxoids and to find out whether these two modifications are cooperative at the binding site in the ß-tubulin or not, as well as to see how these effects are reflected in the biological activities of the new 3rd-generation DFV-taxoids. Accordingly, we designed, synthesized and fully characterized 14 new 3rd-generation DFV-taxoids. These new DFV-taxoids exhibited remarkable cytotoxicity against human breast, lung, colon, pancreatic and prostate cancer cell lines. All of these new DFV-taxoids exhibited subnanomolar IC50 values against drug-sensitive cell lines, A549, HT29, Vcap and PC3, as well as CFPAC-1. All of the novel DFV-taxoids exhibited 2-4 orders of magnitude greater potency against extremely drug-resistant cancer cell lines, LCC6-MDR and DLD-1, as compared to paclitaxel, indicating that these new DFV-taxoids can overcome MDR caused by the overexpression of Pgp and other ABC cassette transporters. Dose-response (kill) curve analysis of the new DFV-taxoids in LCC6-MDR and DLD-1 cell lines revealed highly impressive profiles of several new DFV-taxoids. The cooperative effects of the combination of the 3'-DFV group and 3-CF3O/CHF2O-benzoyl moiety at the C2 position were investigated in detail by molecular docking analysis. We found that both the 3'-DFV moiety and the 3-CF3O/3-CHF2O group of the C2-benzoate moiety are nicely accommodated to the deep hydrophobic pocket of the paclitaxel/taxoid binding site in the ß-tubulin, enabling an enhanced binding mode through unique attractive interactions between fluorine/CF3O/CHF2O and the protein beyond those of paclitaxel and new-generation taxoids without bearing organofluorine groups, which are reflected in the remarkable potency of the new 3rd-generation DFV-taxoids.

Effects of different selenium sources on duodenum and jejunum tight junction network and growth performance of broilers in a model of fluorine-induced chronic oxidative stress.

The protective effects and underlying molecular mechanisms of sodium selenite (SS) and selenomethionine (SM) against chronic oxidative stress-induced duodenum and jejunum tight junction (TJ) network disturbance and growth inhibition of broilers were investigated in the current experiment. At the age of 1 d, 720 Lingnan Yellow broiler chicks were allocated to 4 experimental diets (with 6 replicates per diet and 30 birds per replicate) and offered either a control diet (fluorine [F] 23 mg/kg, control [CoN] group) or test diets (800 mg/kg F, high F [HF] group; 800 mg/kg F+0.15 mg selenium [Se]/kg as SS [SS group] or SM [SM group]) for 56 d. The results showed that HF group could induce chronic oxidative stress and subsequently increased (P < 0.05) proinflammatory cytokines levels of duodenum and jejunum in comparison with the CoN group. Increased proinflammatory cytokines levels of HF group promoted myosin light chain kinase (MLCK) transcription, thus leading to a decrease (P < 0.05) in TJ proteins expression of duodenum and jejunum when compared with the CoN group. A reduction of TJ proteins expression destroyed the TJ structures in the HF group, which in turn increased intestinal mucosal permeability of duodenum and jejunum and ultimately induced growth inhibition of broilers. Dietary Se supplementation could ameliorate HF-induced duodenum and jejunum TJ network impairment and growth retardation of broilers, potentially by increasing (P < 0.05) the glutathione peroxidase and thioredoxin reductase activities, reducing (P < 0.05) the reactive oxygen species and malondialdehyde levels, regulating the secretion of proinflammatory cytokines, and mediating the transcription level of MLCK in the duodenum and jejunum. Additionally, our data also suggested that the protective effects of SM were superior to those of SS. This study will provide a theoretical basis for developing SM into an efficient protective agent for intestinal mucosal barrier in poultry.

Design, synthesis and antiproliferative activity evaluation of fluorine-containing chalcone derivatives.

A series of new chalcones containing fluoro atom at B ring have been designed, synthesized, and evaluated to be antiproliferative activity against a panel of human tumor cell lines. Some of the analogs (8, 9, 12, 45, 46 and 48) displayed powerful antiproliferative effects to certain human tumor cells, but all of them were devoid of any cytotoxicity towards the normal HEK 293. Acridine orange staining data supported that the cytotoxic and antiproliferative effects of the synthesized analogs on tumor cells are mediated through apoptosis. The compounds 12 and 46 manifested concentration-dependent antiproliferative activity in human hepatocellular carcinoma cell lines using an xCELLigence assay. The structures and antiproliferative activity relationship were further supported by in silico molecular docking study of the compounds against tubulin protein which suggests our compounds interference to cell division. Communicated by Ramaswamy H. Sarma.

Synthesis, Cytotoxicity Evaluation and Molecular Docking of Fluorine Containing Hexahydroquinoline-3-Carbonitrile Derivatives.

BACKGROUND: Fluorine containing hexahydroquinoline-3-carbonitrile derivatives were found to have potent cytotoxicity. Furthermore, fluorine can modulate pharmacokinetic and pharmacodynamic profile of drugs. Hence, new derivatives containing fluorine were explored as potential cytotoxic agents. OBJECTIVE: Difluoro substituted compounds containing aromatic/heteroaromatic rings were designed, synthesized and screened for in vitro cytotoxicity on cancer cell lines. The active compounds were subjected to docking on Mcl-1 and ADME/T prediction. METHODS: The synthesized compounds were characterized using various spectral techniques like FT-IR, 1H NMR, 13C NMR and Mass spectra. Compounds were screened for cytotoxicity on NCI-60 cell lines at the National Cancer Institute. The active compounds were evaluated additionally by MTT and SRB assay. RESULTS: Compounds (6l and 6o) showed maximum cytotoxicity with (% GI) of 69 and 63.7 at 10 µM drug concentration, respectively. Compound 6i showed potent cytotoxicity with GI50 of 7.2 µM against Ishikawa cell line. Compound 6o was nearly as active as a reference with IC50 of 9.39 µM and 13.54 µM against HT-29 and HCT-116, respectively, and compound 6l also showed equal potency to that of reference with IC50 of 9.66 µM against Caco-2. Compounds 6i, 6o and 6l showed high docking scores, suggesting their cytotoxicity. Furthermore, ADME/T prediction revealed that all the compounds had drug-likeness properties. CONCLUSION: Enhanced lipophilic interaction of compounds due to the presence of fluorine in compounds 6i and 6l was revealed during the docking study. Compound 6i can be explored as a lead molecule against other endometrial cancer in futuristic drug development.

The Effects of Sodium Fluoride (NaF) Treatment on the PI3K/Akt Signal Pathway in NRK-52E Cells.

The effects of the element fluorine on the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathway has a significant role in regulation of intracellular molecular mechanisms. NRK-52E rat kidney epithelial cell line was selected as the material of the study. NaF was used as the fluorine source in the study. The NaF dose was determined with the MTT assay. The NaF concentrations were determined as the proliferation concentration of 10 µM and IC25 (2250 µM) and IC50 (4250 µM) for 24 h. In the study, the erb-b2 receptor tyrosine kinase 2 (ERBB2), phosphoinositide-3-kinase (PI3K), Protein kinase B (PKB,Akt), Mammalian target of rapamycin (mTOR), and the Tumor protein 53 (TP53) genes were considered as the target genes. NaF concentration was administered on the cells. Total mRNA was isolated. mRNAs were turned into cDNA. The expression levels of the target genes were determined by RT-qPCR method. According to the results obtained in the study, the low NaF concentration increased the expression levels of the ERBB2, PI3K, and Akt genes, while the higher concentrations did not significantly affect these levels. The expression of mTOR decreased at all given concentrations. The expression of the TP53 gene did not change at the low concentration, while it increased at the high concentrations. Based on the results, it may be stated that fluorine may inhibit the kinase enzymes in the PI3K/Akt pathway. In summary, in the pathogenesis of the cell damage caused by fluorine in the NRK-52E cell line, the PI3K/Akt/mTOR pathway is an important signal pathway.

Novel symmetrical and unsymmetrical fluorine-containing metallophthalocyanines: synthesis, characterization and investigation of their biological properties.

In this study, a new fluorinated phthalonitrile compound namely 5-bis[4-(trifluoromethoxy)-thiophenyl] phthalonitrile was synthesized. In addition, peripherally substituted symmetric metallated phthalocyanine derivatives [M = Co (2) and M = Zn (3)] and unsymmetrically substituted zinc phthalocyanine (ZnPc) complex (4) were synthesized by cyclotetramerization of this phthalonitrile compound. Characterization of all new compounds was carried out using FT-IR, NMR, UV-Vis, and mass spectroscopy. Additionally, antioxidant activity, DNA cleavage activity, antimicrobial activity, biofilm inhibition activity, and bacterial viability inhibition test of the compounds (1-4) were investigated. The antioxidant activities of the new phthalocyanine complexes were studied by performing two different methods. The results indicated that the highest DPPH (1,1-diphenyl-2-picrylhydrazyl) free radical scavenging activity was determined to be 67.85% for 2 and also 3 showed the highest activity with 31.65% for chelating activity at 200 mg L-1 concentration. Phthalocyanine compounds demonstrated effective DNA cleavage and antimicrobial activities. The highest percentage of cell vitality inhibition was found for compound 4, 56.92%. Also, test compounds exhibited good biofilm inhibition activity.

The Effects of Calcium, Magnesium, Phosphorus, Fluoride, and Lead on Bone Tissue.

Bones are metabolically active organs. Their reconstruction is crucial for the proper functioning of the skeletal system during bone growth and remodeling, fracture healing, and maintaining calcium-phosphorus homeostasis. The bone metabolism and tissue properties are influenced by trace elements that may act either indirectly through the regulation of macromineral metabolism, or directly by affecting osteoblast and osteoclast proliferation or activity, or through becoming part of the bone mineral matrix. This study analyzes the skeletal impact of macroelements (calcium, magnesium, phosphorus), microelements (fluorine), and heavy metals (lead), and discusses the concentration of each of these elements in the various bone tissues.

Do Only Calcium and Vitamin D Matter? Micronutrients in the Diet of Inflammatory Bowel Diseases Patients and the Risk of Osteoporosis.

Osteoporosis is one of the most common extraintestinal complications among patients suffering from inflammatory bowel diseases. The role of vitamin D and calcium in the prevention of a decreased bone mineral density is well known, although other nutrients, including micronutrients, are also of extreme importance. Despite the fact that zinc, copper, selenium, iron, cadmium, silicon and fluorine have not been frequently discussed with regard to the prevention of osteoporosis, it is possible that a deficiency or excess of the abovementioned elements may affect bone mineralization. Additionally, the risk of malnutrition, which is common in patients with ulcerative colitis or Crohn's disease, as well as the composition of gut microbiota, may be associated with micronutrients status.