Sci. Pharm., Volume 79, Issue 2 (June 2011) – 13 articles , Pages 225-388

Sulfonamide substituted 8-hydroxyquinoline derivatives were prepared using a microwave synthesizer. The interaction of sulfonamide substituted 8-hydroxyquinoline derivatives and their transition metal complexes with Plasmid (pUC 19) DNA and Calf Thymus DNA were investigated by UV spectroscopic studies and gel electrophoresis measurements. The interaction between ligand/metal complexes and DNA was carried out by increasing the concentration of DNA from 0 to 12 μl in UV spectroscopic study, while the concentration of DNA in gel electrophoresis remained constant at 10 μl. These studies supported the fact that, the complex binds to DNA by intercalation via ligand into the base pairs of DNA. The relative binding efficacy of the complexes to DNA was much higher than the binding efficacy of ligands, especially the complex of Cu-AHQMBSH had the highest binding ability to DNA. The mobility of the bands decreased as the concentration of the complex was increased, indicating that there was increase in the interaction between the metal ion and DNA. Complexes of AHQMBSH were excellent for DNA binding as compared to HQMABS. Full article

The inhibition of tumor angiogenesis has become a compelling approach in the development of anticancer drugs. In the present study, topological models were developed through decision tree and moving average analysis using a data set comprising 42 analogues of 3-aminoindazoles. A total of 22 descriptors (distance based, adjacency based, pendenticity and distance-cum-adjacency based) were used. The values of all 22 topological indices for each analogue in the dataset were computed using an in-house computer program. A decision tree was constructed for the receptor tyrosine kinase KDR (kinase insert domain receptor) inhibitory activity to determine the importance of topological indices. The decision tree learned the information from the input data with an accuracy of 88%. Three independent topological models were also developed for prediction of receptor tyrosine kinase inhibitory (KDR) activity using moving average analysis. The models developed were also found to be sensitive towards the prediction of other receptor tyrosine kinases i.e. FLT3 (fms-like tyrosine kinase-3) and cKIT inhibitory activity. The accuracy of classification of single index based models using moving average analysis was found to be 88%. The performance of models was assessed by calculating precision, sensitivity, overall accuracy and Mathew’s correlation coefficient (MCC). The significance of the models was also assessed by intercorrelation analysis. Full article

Lysozyme is one of the most important factors of innate immunity and a unique enzybiotic in that it exerts not only antibacterial activity, but also antiviral, antiinflammatory, anticancer and immunomodulatory activities. The purpose of the present study was to investigate whether in vitro exposure to saponins can affect the release and production of lysozyme activity in human monocytic cells THP-1, and in human epithelial cells HT-29. Lysozyme activity levels in cell culture fluids were measured using highly sensitive fluorescence-based lysozyme activity assay. Majority of the examined saponins were demonstrated to stimulate significantly the release of lysozyme activity of monocytes and epithelial cells after one hour treatment at non-toxic concentrations. On the contrary, cells treated with saponins for longer periods up to 72 hours showed tendency to decrease in the secretion and production of lysozyme activity. However, these inhibitory effects of saponins observed with long-term treatment periods were mostly associated with toxic effects of saponins to cells. The results suggested positive contribution of some saponins to lysozyme release of monocytes and epithelial cells upon short exposure. Furthermore, demonstrated ability of these saponins to enhance the release of lysozyme activity can present a new mechanism contribute to explaining important biological characteristics of saponins, including the antibacterial, antiviral, antiinflammatory or immune-stimulating properties. Full article

A solid dispersion of Meloxicam (MX), a poorly soluble, non steroidal antiinflammatory drug, and Gelucire 50/13 was prepared by spray drying. Spherical microparticles were yielded with smooth surfaces as observed by scanning electron microscopy. According to differential scanning calorimetry and powder X-ray diffractometry analysis, MX was transformed from the crystalline state to the amorphous state as confirmed by the disappearance of its melting peak and the crystalline peaks. The dissolution tests at pH 7.4 revealed that the dissolution rate of encapsulated MX was 2.5-fold higher than that of the corresponding physical mixture and fourfold higher than the drug alone, respectively. The microparticles prepared at a ratio of 1:4 (drug/Gelucire) exhibited a 4-fold higher anti-inflammatory activity on the paw edema of rats in comparison to the drug alone. All in all, this work reveals that spray drying is a suitable technique for preparation of solid dispersions with improved biopharmaceutical and pharmacological characteristics of MX. Full article

Plants of the genus Crinum (Amaryllidaceae) are widely used in folk medicine in different tropical and subtropical regions around the world. The Indian species Crinum latifolium (L.) was traditionally used to treat rheumatism, fistula, tumors, earaches, rubefacient, tubercle and whitlow. In Vietnamese and Chinese traditional medicine Crinum latifolium preparations are used until nowadays because of their antiviral and antitumor properties. In this study, we demonstrate potent in vitro antioxidant activity of an aqueous Crinum latifolium extract by an oxygen radical absorbance capacity (ORAC) value of 1610 ± 150 μmol Trolox equivalents/g. Furthermore, significant anti-inflammatory effects of this extract were shown by its potential to suppress indoleamine 2,3-dioxygenase (IDO) mediated tryptophan degradation in unstimulated- and mitogen-stimulated PBMC at IC₅₀ doses of 241 ± 57 μg/ml and 92 ± 20 μg/ml, respectively. Concentrations of the immune activation marker neopterin were slightly diminished in unstimulated PBMC, whereas a dose-dependent inhibition of neopterin formation was observed in mitogen-stimulated PBMC (IC₅₀ = 453 ± 86 μg/ml). Additionally, we measured also dose-dependent inhibitory effects of this aqueous Crinum latifolium extract on cell proliferation of highly metastatic human prostate carcinoma PC3 cells (IC₅₀ = 4.5 ± 0.8 mg/ml), androgensensitive prostate adenocarcinoma LNCaP cells (IC₅₀ =2.3 ± 0.1 mg/ml), and benign prostate hyperplasia BPH-1 cells (IC₅₀ = 2.1 ± 0.04 mg/ml). We conclude that both effects, inhibition of tumor cell growth and recovery of immune functions, are important for the antitumor properties of Crinum latifolium. Full article

Ibuprofen–polyethylene glycol (PEG) conjugates (PEG-Ibu) were prepared and their potential as a prolonged release system was investigated. Two PEG-Ibu conjugates were synthesized from Ibuprofen and PEG with two different molecular weights by esterification in the presence of DCC and DMAP. The PEG-Ibu conjugates were characterized by FT-IR, 1H NMR, Mass spectroscopy and DSC analysis. The solubility study in aqueous system showed an increase in solubility of conjugates. The dissolution / hydrolysis studies showed a specific acid–base catalysis pattern dependent on the pH of the medium. This indicated a good chemical stability in aqueous buffer solution of acidic medium and the extended release behavior was found in both prodrugs after 9 hour. The results demonstrate that, in the same condition, the rate of hydrolysis for PEG4000-Ibu is slower than other. The Writhing induced by acetic acid experiment and paw edema test after oral administration showed that both conjugates had extended analgesic and anti-inflammatory effects compared with Ibuprofen. These results suggest that PEG-Ibu could be a promising NSAID prodrug with an extended pharmacological effect owing to delayed-release of parent drug. Full article

The aim of the present study was the development of thermo-sensitive in-situ gels for in-vitro evaluation of ophthalmic delivery systems of ketorolac tromethamine (KT), based on methylcellulose (MC) in combination with hydroxypropylmethyl cellulose (HPMC). The gel temperature of 1% MC solution was observed at 60°C. It was found that 6% oral rehydration salt without dextrose (ORS) was capable to reduce the gel temperature below physiological temperature. HPMC was added to increase viscosity and drug release time. The results indicated a large increase in viscosity at 37°C with addition of HPMC whch provided sustained release of the drug over a 4h period. From in-vitro release studies, it could be concluded that the developed systems were thus a better alternative to conventional eye drops. Full article

In the search for new and effective prodrugs against the herpes simplex virus, a series of acyclovir analogues with a thiazole ring containing amino acids (glycine, alanine, valine, leucine) has been investigated. The chemical stability of some of the compounds containing different residues was studied at pH 1 and pH 7.4 at a temperature of 37°C. An HPLC method was developed for quantification of the unchanged ester concentration. Some of the esters (Gly-thiazole, Ala-thiazole-acyclovir, Leu-thiazole-acyclovir) were rather unstable, especially under acidic conditions, and underwent rapid hydrolysis into the chemical precursor acyclovir. At pH 7.4, the stability of Valthiazole- acyclovir was remarkable. At this pH, Val-thiazole-acyclovir showed stability higher than that of valacyclovir (the first effective prodrug of acyclovir). Full article

Development of lanthanide detoxification agents and protocols is of great importance in management of overdoses. Due to safety of maltol as a detoxifying agent in metal overloads, it can be used as a lanthanide detoxifying agent. In order to demonstrate the biodistribution of final complex, [¹⁵³Sm]- samarium maltolate was prepared using Sm-153 chloride (radiochemical purity >99.9%; ITLC and specific activity). The stability of the labeled compound was determined in the final solution up to 24h as well as the partition coefficient. Biodistribution studies of Sm-153 chloride, [¹⁵³Sm]-samarium maltolate were carried out in wild-type rats comparing the critical organ uptakes. Comparative study for Sm³⁺ cation and the labeled compound was conducted up to 48 h, demonstrating a more rapid wash out for the labeled compound. The effective and biological half lives of 2.3 h and 2.46h were calculated for the complex. The data suggest the detoxification property of maltol formulation for lanthanide overdoses. Full article

A selective, specific and stability-indicating gradient reverse phase highperformance liquid chromatographic (HPLC) method was developed for the determination of Ranitidine in presence of its impurities, forced degradation products and placebo substances such as saccharide and parabens. Ultraviolet detection was performed at 230 nm. Separate portions of the drug product and ingredients were exposed to stress conditions to induce oxidative, acidic, basic, hydrolytic, thermal and photolytic degradation. Ranitidine was found to degrade significantly at acidic, basic and oxidative stress conditions but was stable at heat and humidity. The developed method was validated as per International Conference on Harmonization (ICH) guidelines. The method was validated over this range for (i) system suitability (ii) specificity, (iii) precision, (iv) limit of detection and limit of quantification, (v) linearity, (vi) accuracy, (vii) robustness. The method was found to be precise, accurate, linear and robust. The proposed method was successfully employed for estimation of Ranitidine impurities in pharmaceutical preparations. Full article

An improved gradient, reversed-phase liquid chromatographic (RP-LC) method was developed and subsequently validated for the determination of Loratadine and its impurities/degradation products in pharmaceutical drug substance. Separation was achieved with Inertsil ODS-3V, 250 x 4.6 mm, 5μ column with gradient elution at a flow rate of 1.0 mL min⁻¹. UV detection was performed at 220 nm. The described method is linear over a range of LOQ (0.044, 0.088, 0.084, and 0.072 μg mL⁻¹ for impurity-B, impurity-C, impurity-D, and impurity-E respectively) to 1.2 μg mL⁻¹ (0.6 μg mL⁻¹ of the specification limit) for all the impurities and degradation products. The recovery of impurities were found to be in the range of 85–115 %. The method is simple, selective, and accurate for the quantification of impurities and degradation products of Loratadine in its bulk drug samples. Full article

A set of 13 alkyl derivatives of 3-phenylpiperidine-2,6-dione were synthesized. Newly obtained compounds were investigated in vitro against HIV-1 and other selected viruses. The benzyl 3f and fluorophenyl 3g derivatives showed moderate protection against CVB-2 and the compound 3g also against HSV-1. Derivatives were tested also for their antibacterial and antifungal activity. The molecular structures of 3a and 3d were determined by an X-ray analysis. Full article