Rational Design and Synthesis of Naphthalene Diimide Linked Bis-Naphthalimides as DNA Interactive Agents.

A molecular modeling assisted rational design and synthesis of naphthalene diimide linked bis-naphthalimides as potential DNA interactive agents is described. Chemical templates incorporating naphthalene diimide as a linker in bis-naphthalimide motif were subjected to molecular docking analysis at specific intercalation and telomeric DNA G-quadruplex sites. Excellent results were obtained, which were better than the standards. A short and convenient synthetic route was employed to access these hybrids experimentally, followed by evaluation of their ability to cause thermal denaturation of DNA and cytotoxic properties along with ADME predictions. The obtained results provided useful insights and two potential molecules were identified for further development.

Enhanced Antimicrobial Activity of Biofunctionalized Zirconia Nanoparticles.

The effective interactions of nanomaterials with biological constituents play a significant role in enhancing their biomedicinal properties. These interactions can be efficiently enhanced by altering the surface properties of nanomaterials. In this study, we demonstrate the method of altering the surface properties of ZrO2 nanoparticles (NPs) to enhance their antimicrobial properties. To do this, the surfaces of the ZrO2 NPs prepared using a solvothermal method is functionalized with glutamic acid, which is an α-amino acid containing both COO- and NH4 + ions. The binding of glutamic acid (GA) on the surface of ZrO2 was confirmed by UV-visible and Fourier transform infrared spectroscopies, whereas the phase and morphology of resulting GA-functionalized ZrO2 (GA-ZrO2) was identified by X-ray diffraction and transmission electron microscopy. GA stabilization has altered the surface charges of the ZrO2, which enhanced the dispersion qualities of NPs in aqueous media. The as-prepared GA-ZrO2 NPs were evaluated for their antibacterial properties toward four strains of oral bacteria, namely, Rothia mucilaginosa, Rothia dentocariosa, Streptococcus mitis, and Streptococcus mutans. GA-ZrO2 exhibited increased antimicrobial activities compared with pristine ZrO2. This improved activity can be attributed to the alteration of surface charges of ZrO2 with GA. Consequently, the dispersion properties of GA-ZrO2 in the aqueous solution have increased considerably, which may have enhanced the interactions between the nanomaterial and bacteria.

Identification of nanoscale ingredients in commercial food products and their induction of mitochondrially mediated cytotoxic effects on human mesenchymal stem cells.

Titanium dioxide (E171) and silicon dioxide (E551) are common additives found in food products, personal-care products, and many other consumer products used in daily life. Recent studies have reported that these food additives (manufactured E171 and E551) contain nanosized particles of less than 100 nm. However, the particle size distribution and morphology of added TiO2 and SiO2 particles are not typically stated on the package label. Furthermore, there is an increasing debate regarding health and safety concerns related to the use of synthetic food additives containing nanosized ingredients in consumer products. In this study, we identified the size and morphology of TiO2 and SiO2 particles in commercially available food products by using transmission electron microscope (TEM). In addition, the in vitro toxicological effects of E171 and E551 on human mesenchymal stem cells (hMSCs), an adult stem cell-based model, were assessed using the MTT assay and a flow cytometry-based JC-1 assay. Our TEM results confirmed the presence of nanoscale ingredients in food products, and the in vitro toxicology results indicated that the nanoscale E171 and E551 ingredients induced dose-dependent cytotoxicity, changes in cellular morphology, and the loss of mitochondrial trans-membrane potential in hMSCs. These preliminary results clearly demonstrated that the nanoscale E171 and E551 particles had adverse effects on hMSCs by inducing oxidative stress-mediated cell death. Accordingly, further studies are needed to identify the specific pathway involved, with an emphasis on differential gene expression in hMSCs.

Presence of nanosilica (E551) in commercial food products: TNF-mediated oxidative stress and altered cell cycle progression in human lung fibroblast cells.

Silica (E551) is commonly used as an anti-caking agent in food products. The morphology and the dimension of the added silica particles are not, however, usually stated on the food product label. The food industry has adapted nanotechnology using engineered nanoparticles to improve the quality of their products. However, there has been increased debate regarding the health and safety concerns related to the use of engineered nanoparticles in consumer products. In this study, we investigated the morphology and dimensions of silica (E551) particles in food. The silica content of commercial food products was determined using inductively coupled plasma optical emission spectrometry. The result indicates that 2.74-14. 45 µg/g silica was found in commercial food products; however, the daily dietary intake in increase causes adverse effects on human health. E551 was isolated from food products and the morphology, particle size, crystalline nature, and purity of the silica particles were analyzed using XRD, FTIR, TEM, EDX and DLS. The results of these analyses confirmed the presence of spherical silica nanoparticles (of amorphous nature) in food, approximately 10-50 nm in size. The effects of E551 on human lung fibroblast cell viability, intracellular ROS levels, cell cycle phase, and the expression levels of metabolic stress-responsive genes (CAT, GSTA4, TNF, CYP1A, POR, SOD1, GSTM3, GPX1, and GSR1) were studied. The results suggest that E551 induces a dose-dependent cytotoxicity and changes in ROS levels and alters the gene expression and cell cycle. Treatment with a high concentration of E551 caused significant cytotoxic effects on WI-38 cells. These findings have implications for the use of these nanoparticles in the food industry.

Electrochemical determination of Cephalothin antibiotic by adsorptive stripping voltammetric technique.

A sensitive and reliable stripping voltammetric method was developed to determine Cephalothin antibiotic drug. This method is based on the adsorptive accumulation of the drug at a hanging mercury drop electrode and then a negative sweep was initiated, which yield a well defined cathodic peak at -625 mV versus Ag/AgCl reference electrode. To achieve high sensitivity, various experimental and instrumental variables were investigated such as supporting electrolyte, pH, accumulation time and potential, drug concentration, scan rate, convection rate and working electrode area. The monitored adsorptive current was directly proportional to the concentration of Cephalothin and it shows a linear response in the range from 4 x 10(-7) to 1.2 x 10(-6) mol l(-1) (correlation coefficient=0.9995) and the detection limit (S/N=3) is 3.3 x 10(-9) mol l(-1) at an accumulation time of 3 min. The developed AdSV procedure shows a good reproducibility, the relative standard deviation R.S.D.% (n=10) at a concentration level of 5 x 10(-7) mol l(-1) was 0.94%. Possible interferences by other pharmaceutical drugs and surfactants have been also evaluated. The applicability of this approach was illustrated by the determination of Cephalothin in pharmaceutical preparation and biological fluids such as serum and urine.