Search

Cancer is a disease that occurs as a result of abnormal or uncontrolled growth of cells due to DNA damage, among many other causes. Certain cancer treatments aim to increase the excess of DNA breaks to such an extent that they cannot escape from the general mechanism of cell checkpoints, leading to the apoptosis of mutant cells. In this study, one of the Sarco-endoplasmic reticulum Ca2+ATPase (SERCA2a) inhibitors, Istaroxime, was investigated. There has been very limited number of articles so far reporting Istaroxime's anticancer activity; thus, we aimed to evaluate the anticancer effects of Istaroxime by cell proliferation assay and revealed the cytotoxic activity of the compound. We further determined the interaction of Istaroxime with topoisomerase enzymes through enzyme activity tests and detailed molecular modeling analysis. Istaroxime exhibited an antiproliferative effect on A549, MCF7, and PC3 cell lines and inhibited Topoisomerase I, suggesting that Istaroxime can act as a Topoisomerase I inhibitor under in vitro conditions. Molecular docking analysis supported the experimental observations. A chemical reactivity analysis of the Istaroxime molecule was made in the light of Density Functional Theory computations. For this aim, important chemical reactivity descriptors such as hardness, electronegativity, and electrophilicity were computed and discussed as detailed. [ABSTRACT FROM AUTHOR]

1,2‐Phenylenediamine (o‐PDA) is a well‐known fluorescent dye that enables the decoration of next‐generation chemotherapeutics. A novel o‐PDA‐functionalized maleic anhydride‐allyl phenyl ether (poly(MA‐alt‐APE)/o‐PDA conjugate) was successfully synthesized according to the Ringsdorf model, which is the starting point for macromolecular prodrugs. Functional polymeric‐carriers were prepared by free‐radical polymerization in butyl acetate with azobisisobutyronitrile (AIBN) radical‐initiator at 70 °C. The conjugation was carried out at 40 °C in N,N‐dimethylformamide (DMF) using triethylamine (Et3N) as the conjugation catalyst. Characterization was performed by Attenuated Total Reflectance‐Fourier Transform Infrared (ATR‐FTIR), Nuclear Magnetic Resonance (1H‐NMR), UV‐Vis and Fluorescence Spectroscopy. Weight average molecular weight (Mw), number average molecular weight (Mn) and polydispersity index (PDI) (Mw/Mn) were calculated using gel permeation chromatography (GPC). The surface morphology was also elucidated by Transmission Electron Microscopy (TEM). Evaluation of antimicrobial activity against two Gram‐positive bacteria (Staphylococcus aureus, Bacillus cereus), two Gram‐negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and one yeast Candida albicans was performed using the broth microdilution method according to Clinical Laboratory Standards Institute (CLSI) criteria. Interestingly, S. aureus was found to be more sensitive to polymer‐based samples and, in particular, the minimum inhibitory concentration (MIC) of the conjugate was lower than that of ciprofloxacin used as a control compound. [ABSTRACT FROM AUTHOR]

In recent years, polymeric drug conjugates, nanoparticles, nanocapsules, liposomes, micelles, dendrimers, and nanogels have been gained a great attention. Organically modified layered nanoclays have become an attractive hybrid biomaterial due to their wide range of uses, which can be designed with desired properties in a wide variety of applications from industry to medicine. Functional water‐soluble poly(maleic anhydride‐alt‐acrylic acid) [poly(MA‐alt‐AA)], synthesized in our previous study, was chosen for the prepare of halloysite/polymer nanocomposite. Surface modification of halloysite nanotubes (HNTs) with 3‐aminopropyltriethoxysilane (APTS) was performed to obtain organic functionalized halloysite and also for better compatibility of nanotubes (NTs) with monomers. Nanocomposite were obtained by in situ solution complex‐radical copolymerization via charge transfer complex under conditions of copolymerization, using pristine and APTS functionalized HNTs, acrylic acid (AA), and maleic anhydride (MA) monomers. Optimization study using different clay ratios and recipe for organic–inorganic compatibility also were carried out. Characterization studies of halloysite, modified halloysite, copolymers and the formed copolymer‐HNT nanotubes were enlighten by using spectroscopic analyzes such as, Attenuated Total Reflectance‐Fourier Transform Infrared Spectroscopy (ATR‐FTIR), High resolution Raman (HR‐Raman), X‐Ray Diffraction Measurements (XRD) and X‐Ray Photoelectron Spectroscopy (XPS). Thermal analysis and dynamic mechanical properties were performed with Thermogravimetric Analysis (TGA) and Dynamic Mechanical Analysis (DMA), respectively. Surface morphology was also carried out by Transmission Electron Microscopy (TEM). In the light of these detailed analysis results, it can be briefly concluded that surface modification of HNT, synthesis of copolymer/HNT nanocomposites, and structural characterization successfully achieved. [ABSTRACT FROM AUTHOR]

This study includes the design, synthesis and characterization of 1,2-phenylenediamine (o-PDA) functionalized maleic anhydride (MA)-vinyl acetate (VA) copolymer-based conjugate to develop a new formulation. The phenylenediamine molecule is a fluorescent dye that allows designing new chemotherapeutic polymeric molecules. Poly(maleic anhydride-alt-vinyl acetate) [Poly(MA-alt-VA)] was obtained via charge transfer complex (CTC) radical polymerization presence of methyl ethyl ketone (MEK), utilizing benzoyl peroxide (BPO) free-radical initiator at 80 °C, as a potential functional polymeric carrier. Structural characterization of the surface functionalized poly(MA-alt-VA)/1,2-PDA conjugate was performed by Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) and Nuclear Magnetic Resonance (1H-NMR). Spectroscopic methods and water solubility results confirmed that the conjugation took place successfully after the ring opening reaction by the amide mechanism. [ABSTRACT FROM AUTHOR]

Background: Although there have been a number of studies on the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) recently, knowledge on this topic is still insufficient. This study aims to reveal the kinetics of serum CCHF virus (CCHFV) titers, serum levels of anti-CCHFV immunoglobulin (Ig)G, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and interferon (IFN)-γ in CCHF patients. Methods: In total, 31 CCHF cases (11 fatal) were studied. Serum samples were obtained daily from all patients from the time of admission and continued for a 7-day hospitalization period for serologic (ELISA), virologic (real-time PCR), and cytokine (ELISA) analysis. Results: The mean serum CCHFV titer at admission was 5.5E + 09 copies/mL in fatal cases and 5.7E + 08 copies/mL in survivors (p < 0.001). Compared to survivors, both the mean serum levels of IL-6 and TNF-α at admission were found to be significantly increased in fatal cases. The serum levels of IL-6, TNF-α and serum CCHFV titer at admission were significantly and positively correlated with disseminated intravascular coagulation (DIC) scores (r = 0.626, p = 0.0002; r = 0.461, p = 0.009; and r = 0.625, p = 0.003, respectively). When the data obtained from the sequential determination of CCHFV titer and levels of anti-CCHFV IgG, IL-6, TNF-α, IL-10 and IFN-γ were grouped according to the days of illness, the initial serum CCHFV titer of a fatal patient was 5.5E + 09 (copies/mL) and it was 6.1E + 09 (copies/mL) in a survivor on the 2 day of illness. While significant alterations were observed in all cytokines during the monitoring period, IL-6 levels remained consistently higher in fatal cases and TNF-α levels increased in both in fatal and non-fatal CCHF cases. Conclusions: The increased CCHFV load and higher concentrations of IL-6 and TNF-α, the presence of DIC, and the absence of CCHFV specific immunity are strongly associated with death in CCHF. [ABSTRACT FROM AUTHOR]

Poly(maleic anhydride-co-styrene) (MAST) was synthesized by a free-radical polymeriza-tion reaction. A bioactive molecule, procainamide hydrochloride (PH), was then conjugated to MAST. The conjugation product was named as MAST/PH. Structural characterization of MAST and MAST/PH was carried out by Fourier Transform Infrared and Nuclear Mag-netic Resonance spectroscopy. Their molecular weights were determined by size-exclusion chromatography. A mechanism was then suggested for the conjugation reaction. The results of the cytotoxicity assay, employing a mouse fibroblast cell line (L929), indicated that MAST/PH had no cytotoxicity at concentrations <62pgmL~' (p > 0.05). Antiproliferative activities of MAST/PH and PH were determined by the BrdU cell proliferation ELISA assay, using C6 and HeLa cell lines. In the experiment, two anticancer chemotherapy drugs, cisplatin and 5-fluorouracil, were included as positive control. Antiproliferative activity results demonstrated that MAST/PH yielded the highest suppression profile (approximately 42%) at 20p.g/ml, while free PH exerted the same activity at 100pg/ml. Interestingly, both MAST/PH and PH suppressed the proliferation of only one of the cell lines, C6 cells. Both cisplatin and 5-fluorouracil yielded approximately 60% antiproliferative activity on C6 cells at 20 and 100pg/ml concentrations. Antiangiogenic capacity of both MAST and MAST/PH was also investigated by using the chicken chorioallantoic membrane assay. Results obtained indicated that while MAST/PH could be included into the category of good antiangiogenic substances, the activity score of MAST was within the weak category. [ABSTRACT FROM AUTHOR]

Poly[(maleic anhydride)- co-(vinyl acetate)] (MAVA) copolymer was synthesized by free radical polymerization reaction, in methyl ethyl ketone at 80 °C, using benzoyl peroxide as the initiator. The copolymer was then modified with a biomolecule, noradrenaline (NA). The modification reaction was performed at 70 °C in dimethylformamide containing triethylamine as the catalyst. The modified polymer was named MAVA/NA. Structural characterization of the copolymer and the modified product was carried out by Fourier transform infrared (FTIR) and 1H NMR and 13C NMR spectroscopy. The FTIR, 1H NMR and 13C NMR spectra confirmed that NA was successfully covalently bound to the MAVA copolymer backbone. Surface morphology was visualized by atomic force microscopy. The cumulative release of NA from MAVA/NA was determined in phosphate buffered saline solution for 7 days at 37 °C and compared with MAVA. Cytotoxicity of the MAVA/NA was evaluated by using a mouse fibroblast cell line (L929). Results obtained indicated that MAVA/NA had almost no toxicity and no negative effect on cell viability at 250 µg mL−1 concentration. © 2012 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Aim. The aim of this study was to investigate the effect of radiation doses very close to the human dose for oral cancers on mechanical, chemical and physical properties for poly methyl-methacrylate (PMMA). Methods. PMMA samples were divided into four different groups: no irradiated group, 25-Gy irradiated group, 50-Gy irradiated group and 75-Gy irradiated group. Each group contained nine samples. After 24 h, a three-point loading test was applied to each PMMA groups. The transverse strength and the elastic modulus were calculated using the test results. The results were analyzed statistically by using one-way analysis of variance. The structural characterizations of the PMMA samples were carried out by a Fourier Transform Infrared (FTIR) spectrophotometer to evaluate the chemical structure differences. Results. The transverse strength values of 25-Gy, 50-Gy and 75-Gy radiation groups were significantly higher than that of the no radiation group ( p < 0.05). There was no significant difference among the elastic modulus values of the study groups ( p > 0.05). The FTIR findings demonstrated that the irradiation process did not change the chemical structure of the PMMA polymeric materials. Conclusion. The therapeutic radiation doses increase the mechanical properties of the PMMA; however, the chemical and structural properties have no effect. When the findings of this study are taken into account, it can be said that patients can wear dentures during the radiotherapy. [ABSTRACT FROM AUTHOR]

Maleic anhydride copolymer was modified with another biologically active agent, noradrenaline (NA), using both chemical and enzymatic methods. The modification and synthesized products were named as follows: chemical modification, MASTNAc; enzymatic modification, MASTNAe; enzymatically synthesized MASTNA from individual monomers, MASTNAem. Chemical and enzymatic reactions were performed at 70°C and 38°C, respectively. In the chemical reactions azobisisobutyronitrile was used as the initiator. In the enzymatic reactions, an extracellular extract, including an enzyme with peroxidase-like activity, was used. All the reactions were performed in an organic medium, methyl ethyl ketone. Structural characterization of the copolymer and modified copolymer were carried out by Fourier transform infrared (FTIR) and nuclear magnetic resonance (1H NMR). FTIR and 1H NMR spectra confirmed that NA was successfully covalently bound onto the MAST copolymer backbone by both chemical and enzymatic methods. Surface morphology of the samples was studied by scanning electron microscopy. Results obtained indicated that chemical and enzymatic addition of NA to MAST backbone yielded products having quite similar physical and chemical properties. On the other hand, MASTNA-modified copolymer synthesized by individual monomers appeared to be different in its chemical structure. Furthermore, enzymatic modification and synthesis appeared to provide a good alternative method because it required much milder conditions such as low temperature, and better product qualities: higher solubility in water, higher yield and purity. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011 [ABSTRACT FROM AUTHOR]