Journal of Reports in Pharmaceutical Sciences
Volume:1 Issue: 1, Jan-Jun 2012

Apoptosis, or programmed cell death, is an essential physiological process that plays a critical role in development and tissue homeostasis. Caspases, a family of cysteine-dependent aspartate-directed proteases, play a critical role in the initiation and execution of apoptosis. In this study, cytotoxicity and apoptogenic effect of 2-phenyl 4-carboxamide derivatives were evaluated in SKNMC (human neuroblastoma), MCF-7 (human breast adenocarcinoma) and HT-29 (human colon cancer) cell lines. Cell viability was determined by MTT assay. Also, activation of caspase-3 was evaluated by spectrophotometry. The overall cytotoxicity profiles of derivatives demonstrated that the HT-29 cell line has more sensitivity respect to other cell lines. Moreover, our observations indicated that 3-F and 2-F derivatives and 4-Cl derivative increased caspase-3 activation in three carcinoma cell line compared to control. Collectively, these findings suggest that these derivatives are able to induce apoptosis in cancer cell lines.

H-point standard addition method (HPSAM) with simultaneous addition of both analytes in nonaqueous solution was applied for determination of levonorgestrel (LEV) and ethinyl estradiol (EE) in LD and HD tablets. The results showed that, simultaneous determination could be performed with the ratio 1 to 5 of LEV-EE. The LOD for LEV and EE were obtained 5.1×10-7 and 9.6×10-7 M, respectively, and the corresponding values of %RSD (n=4) for LEV and EE were 1.96 and 2.69, respectively. Underworking conditions, the proposed method was successfully applied for simultaneous determination of LEV and EE in several synthetic mixtures and LD and HD tablets.

In this study, a rapid and simple method based on graphite furnace atomic absorption spectrometry (GFAAS) is described for direct determination of arsenic in potassium citrate tablet samples. Pyrolytic graphite tubes were used as atomizers. Nickel nitrate was used as chemical modifier. The ashing and atomization temperature and the concentration of modifier were also optimized. The detection limit of the method was 0/8 ng/ml As in potassium citrate tablet samples.The relative standard deviation for ten determination of a spiked sample with concentration of 30 ng/ml As ranged was 2.2 %. The accuracy of the method was confirmed by the analysis of spiked samples. The linear rang of calibration is in the range of 0.8-80 ng/ml of arsenic.

The development and discovery of new anticancer agents is one of the main goals in medicinal chemistry. The conventional anticancer drugs are concomitant with high incidence of unpleasant side effects like severe gastrointestinal side effects and bone marrow suppression. In recent years, various selective anticancer agents have been emerged like dasatinib. The exact mechanism of dasatinib is the inhibition of c-Src tyrosine kinase. In fact, over-expression of some types of tyrosine kinases such as c-Src have been proved in some neoplastic disorders like breast cancer. As mentioned above, unwanted side effects and also the emergence of resistant tumors are encouraging agents for discovery of new anticancer drugs. Synthesis and in vitro cytotoxicity evaluation of 2-(4-Substituted-benzyl)isoindoline-1,3-dione derivatives (3-7) in T47D breast cancer cell line, proved the acceptable cytotoxic potency of this series. Compound 7 with IC50 = 1 µg/mL was the most active derivative. This compound showed higher activity in comparison with doxorubicin as reference drug. Molecular docking of these compounds as ligand into the active site of c-Src tyrosine kinase demonstrated the high potency for inhibition of the related enzyme. Compound 7 with binding free energy equal to -10.19 KCal/mol and five hydrogen bonds was the most potent inhibitor in comparison with other ligands.

The aberrant assembly of proteins into fibrillar aggregates is accused to be the primary cause of pathogenesis of neurodegenerative diseases. But the structural determinants of protein fibrils that are responsible for cell dysfunction are not yet clear. In the current study, cell culture, spectroscopic techniques as well as theoretical and structural investigations were used to determine the ability of different fibrillar aggregates to impair cell viability. We evaluated two types of amyloid fibrils that efficiently impair cell viability when added to cell culture. Theoretical and structural investigations indicated differences in the hydrophobic characteristics of protein molecules in the fibrils, so that our findings suggest that surface hydrophobicity may be considered as a main determinant of fibrillar assemblies to cause cellular dysfunction and its consequences such as neurodegeneration. Also, the main objective of the present study was to discuss the potential role of peroxidase activity of “heme-amyloid fibril” complex in neurodegenerative disorders onset/progression using the protein-based experimental models. The results of the present study also suggest that oxidative stress may be involved in neurodegenerative cell toxicity via several independent (mechanistic) routes. The data on origin of amyloid-mediated cell dysfunction may help us to postpone/attenuate the onset/extent of irreversible part of neurodegenerative pathogenesis.

The adsorptive behavior of the immunosuppressive agent tacrolimus was studied by cyclic and differential-pulse voltammetry on a hanging mercury drop electrode (HMDE). The drug was accumulated at HMDE and two well-defined peak currents were obtained at -1353 and -1417 mV vs. SCE (saturated KCl) in borate buffer (pH 10.0) + 0.1 KCl solution. A voltammetric procedure was developed for the determination of tacrolimus using differential-pulse adsorptive stripping voltammetry (DPAdSV). The optimum working conditions for determination of the drug were established. The analysis of tacrolimus in pharmaceutical dosage forms was carried out satisfactorily.

In the present study, sodium alginate microparticle for oral delivery of furosemide was designed whether the encapsulation into microparticles might improve the oral absorption of this potent loop diuretic. We described preparation of microspheres based on ionotropic gelation method and characterized its physicochemical properties.To acquire an optimum formulation, a Generalized Regression Neural Networks (GRNN) and a Multi-Layer Perceptron (MLP) were employed. The drug loaded formulation parameters were the input vectors of the GRNN and included the amount of polymer, cross linked agent, volume of external and internal phases. The microparticles drug loading, size and in vitro drug release constitute the output vector of each network. In this way, GRNN and MLP were trained to investigate the functional influence of input variables on the output responses. The results demonstrated that GRNN is promising in providing better solutions for optimization of drug delivery system formulation.The obtained optimum formulation showed a narrow size distribution on an average diameter of 700 ± 50 μm and drug loading of more than 75%. The drug release profile illustrates a sustained released pattern and released percent of about 36% in 2 hour. In vitro drug release rate for microspheres was found to be sustained over 24 hours, obeying Higuchi order kinetic. Furthermore, the results of this paper confirmed that alginate microparticles could be a hopeful carrier for orally administration of furosemide and provides a sustained release property for this potent anti hypertension drug.In addition, the novel formulation design facilitates the optimization and successful development of microsphere formulations for enhanced safe and effective oral drug delivery.

In this study synthesis of nicotinoyl hydrazone derivatives is investigated by introducing the nicotinic acid hydrazide pharmacophore into several molecules and screening for antimycobacterial activity. Benzaldehyde derivatives react with nicotinic acid hydrazide to form nicotinoyl hydrazones. The synthesized compounds were screened against M. tuberculosis H37Rv, clinical isolates of M. tuberculosis and MDR clinical isolates of M. tuberculosis using the proportion test. The minimum inhibitory concentration (MIC) of N''-(4-methylphenyl) nicotinic acid hydrazone and N''-(4-(N,N-dimethyl)phenyl) nicotinic acid hydrazone exhibited activity between 40 and 200 µg/mL and could be a good start point to find new lead compounds against M. tuberculosis.