Research in Pharmaceutical Sciences
Volume:6 Issue: 2, Oct 2011

Quantitative relationships between molecular structure of forty eight aldehyde compounds with their known Cathepsin K inhibitory effects were discovered by partial least squares (PLS) method. Evaluation of a test set of 10 compounds with the developed PLS model revealed that this model is reliable with a good predictability. Since the QSAR study was performed on the basis of theoretical descriptors calculated completely from the molecular structures, the proposed model could potentially provide useful information about the activity of the studied compounds. Various tests and criteria such as leave-one-out cross validation, leave-many-out cross validation, and also criteria suggested by Tropsha were employed to examine the predictability and robustness of the developed model.

Hydroalcoholic extract of Pycnocycla spinosa has spasmolytic effect in vitro and antidiarrhoeal action in vivo. The aim of this research was to separate fractions of total hydroalcoholic extract of P. spinosa guided by their spasmolytic activity. Aerial parts of P. spinosa were extracted with ethanol. The concentrated extract was subjected to column chromatography and thin layer chromatography. Initially four fractions were obtained (F1, F2, F3, and F4) and their spasmolytic activities were determined on ileum contraction induced by KCl (80 mM). The more active fraction was subjected to further isolation and tested to find its most active components. The active component was phytochemically characterized using phytochemical methods including ultraviolet and infrared spectroscopy. Hydroalcoholic extract of P. spinosa (10-320 mg/ml) in a concentration dependent manner inhibited ileum contraction with the IC50 value of 47 ± 8.1 mg/ml (mean ± S.E.M., n=6). Fraction F2 was the most potent inhibitor of ileum contraction (IC50= 3.4 ± 0.33 mg/ml). From five sub-fractions separated from fraction F2 (F2a, F2b, F2c, F2d, and F2e, respectively), F2c was a more active component with the IC50 value of 2.6 ± 0.27 mg/ml. The primary results of target fraction (F2c) showed sugar moiety in its structure or in one of its components. In this research we have isolated pharmacological active fraction which is most likely responsible for antispasmodic action of P. spinosa hydroalcoholic extract.

Reteplase is a segment of tissue plasminogen activator used for the removal of thrombi in blood vessels. In the present study the cloned reteplase gene was used for its expression in competent E. coli. The recombinant plasmid, pET15b/reteplase (rpET-BL21), was transformed into competent E.coli strain BL21 (DE3) cells. Overnight culture of the transformed bacteria was induced by the addition of isopropylthio-ß-Dgalactoside (IPTG) to the final concentrations of 0.25, 0.5, 1 and 1.5 mM. Also, the effects of different temperatures(25, 30, 37 and 39°C), shaking speeds (100, 170 and 190 rpm), and various glucose concentrations (0.25, 0.5, 0.75 and 1 mM) on the expression of reteplase were examined. Samples were analyzed by SDS-PAGE. Maximum amount of protein production was obtained by the addition of 1 mM IPTG at 37°C, 100 rpm of shaking speed in the absence of glucose.

Quinazolinones are interesting molecules with a wide range of biological activities. We prepared a number of quinazolinone derivatives by the condensation of 5-bromo- or 5-nitro-substituted anthranilic acids with chloro-acyl chlorides. Anthranilic acid derivatives were treated with either 3-chloro-propionyl chloride or 4-chloro-butyryl chloride to yield the corresponding N-acyl-anthranilic acids. The resultants were reacted with acetic anhydride to afford the benzoxazinone intermediates, which upon condensation with elected amines in either DMF or ethanol gave the corresponding tricyclic 4(3H)-quinazolinone derivatives. It was found that reactions in DMF produced higher yields.

The anxiolytic effect of the flower of Echium. amoenum was shown in several experimental studies in mice. The present study was aimed to determine whether tolerance develops to anxiolytic action of E. amoenum in mice. NMRI male mice were injected intraperitoneal with hydroalcoholic extract (12.5, 25 and 50 mg/kg) or saline once each day (8 am) for period of 7 days and then tested on light/dark box model. Anxiolytic effect was determined by light/dark box and elevated plus-maze. According to the results, hydroalcohoic extract of E. amoenum when given both acutely and chronically (7 days) at 25 and 50 mg/kg, significantly increased the time in the illuminated zone. The number of transitions in the light/dark apparatus, however, was not significantly altered by the tested doses of the plant. Diazepam at 0.5 and 1 mg/kg produced anxiolytic effect in both model of anxiety, namely, the light/dark box and elevated plus-maze. No tolerance was developed to the anxiolytic effect of E. amoenum extract after 7 days of treatment. Our results suggest that one week treatment with extract of the E. amoenum does not produce tolerance to its anxiolytic action. Longer period of treatment using implant procedure is probably necessary to cause molecular changes in order to induce tolerance.

A simple and reliable reversed-phase high performance liquid chromatographic (HPLC) method was developed, validated and applied for determination of budesonide and its novel synthesized hemiesters in colon specific formulations and dissolution media. The method was employed on a μ-Bondapak C18 column (250 mm × 4.6 mm, 5 µm) at ambient temperature. The mobile phase consisted of acetonitrile: monobasic potassium phosphate containing orthophosphoric acid (55:45, pH 3.2) at a flow rate of 1 ml/min. The UV detection wavelength was set at 244 nm and 50 µL of sample was injected into the HPLC system. Dexamethasone was used as the internal standard. The retention times for internal standard and budesonide were 4.5 and 7.2 min, respectively. The method was linear in the concentration range of 1-20 µg/ml of budesonide (R2 >0.999). Limit of detection and limit of quantitation were 0.05 and 0.5 µg/ml, respectively. The method presented the requisite accuracy, selectivity, sensitivity and precision and showed good resolution for separation of the drug and related derivatives in the presence of excipients. The proposed method was successfully used for analysis of the drug and its derivatives in dissolution media and oral colon specific formulations prepared in our laboratory with enough reproducibility.

A series of 3-hydroxypyridin-4-one derivatives (HPOs) were synthesized and their partition coefficient values (Kpart) were determined. The cytotoxic effects of these iron chelators against Hela cancer cells were also evaluated. The IC50 of HPOs was determined using MTT assay. Among these ligands, compound 4e (Kpart=5.02) with an IC50 of 30 µM and 4f (Kpart=0.1) with an IC50 of 700 µM showed the lowest and highest IC50's, respectively. In conclusion, the introduction of a more hydrophobic functional group (such as butyl in compound 4e) on the nitrogen of pyridinone ring resulted in higher cytotoxic activity of ligands.

Platanus orientalis L. (Platanaceae) is a medicinal tree used in Iranian folklore and traditional medicine as a pain and inflammation reliever. In this study, the polyphenolic and total extract of P. orientalis leaves were prepared and their antinociceptive effects were studied in mice using the acetic acid-induced writhing, formalin and light tail flick tests. Both hydroalcoholic and polyphenolic extracts of P. orientalis at a dose of 2 g/kg significantly (p<0.05) reduced acetic acid-induced abdominal writhes. These extracts were also effective in suppression of formalin-induced pain behavior but they did not show any significant analgesia in light tail flick test. It is concluded that P. orientalis extracts have moderate analgesic effect and further studies are needed to elucidate the mechanism and active constituents.