Scientia Pharmaceutica

143 KiB

Open AccessEditorial

Scientia Pharmaceutica, Autorenhinweise 2014

by Scientia Pharmaceutica Editorial Office

Sci. Pharm. 2014, 82(1), 207-220; https://doi.org/10.3797/scipharm.aut-14-01 - 8 Feb 2014

Viewed by 1101

Die Zeitschrift Scientia Pharmaceutica (www.scipharm.at) erscheint vierteljährlich jeweils am Quartalsende und ist ein Medium zur Publikation von Originalarbeiten [...] Full article

963 KiB

Open AccessArticle

Lectin-Grafted PLGA Microcarriers Loaded with Fluorescent Model Drugs: Characteristics, Release Profiles, and Cytoadhesion Studies

by Xue-Yan WANG, Romana KOLLER, Michael WIRTH and Franz GABOR

Sci. Pharm. 2014, 82(1), 193-206; https://doi.org/10.3797/scipharm.1312-08 - 8 Feb 2014

Cited by 4 | Viewed by 1507

Abstract

PLGA microparticles loaded with three different fluorescent model drugs, fluorescein sodium (hydrophilic), sulforhodamine (amphoteric), and boron-dipyrromethene (BODIPY^® 493/503, lipophilic), were prepared by the solvent evaporation technique. Due to varying hydrophilicity, the diameters of the microparticles ranged between 4.1 and 4.7 μm. According [...] Read more.

PLGA microparticles loaded with three different fluorescent model drugs, fluorescein sodium (hydrophilic), sulforhodamine (amphoteric), and boron-dipyrromethene (BODIPY^® 493/503, lipophilic), were prepared by the solvent evaporation technique. Due to varying hydrophilicity, the diameters of the microparticles ranged between 4.1 and 4.7 μm. According to fluorimetric analysis, the loading varied from 0.06 to 2.25 μg of the model drug per mg PLGA. In terms of the release profile, the fluorescein sodium-entrapped formulation exhibited thermo-responsive release kinetics. In the case of sulforhodamine- and BODIPY^® 493/503-loaded particles, almost no release was observed, neither at 4°C nor 37°C during the first 50 hours. Furthermore, to estimate the bioadhesive properties of such drug delivery systems, the surface of the loaded particles was grafted with wheat germ agglutinin by applying the carbodiimide method. Cytoadhesion studies with Caco-2 monolayers revealed an up to 1.9-fold and 3.6-fold increase in the bioadhesion of the lectin-functionalized, model drug-loaded particles as compared to the albumin- and non-grafted microcarriers, respectively. All in all, the results clearly indicated that the lipophilicity of the polymer matching that of the drug favored entrapment, whereas mismatching impeded loading into the PLGA-microparticles. Even in the case of low loading, these delivery systems might be useful for the fluorescent detections and microscopic imaging of cellular interactions due to their fluorescent properties and lack of dye leakage. Moreover, lectin grafting can mediate bioadhesive properties to such particulate drug carriers which could be a promising approach to improve drug delivery. Full article

253 KiB

Open AccessArticle

Cytotoxic Sesquiterpene Lactones from Kauna lasiophthalma Griseb

by Eliana M. MALDONADO, Daniel SVENSSON, Stina M. OREDSSON and Olov STERNER

Sci. Pharm. 2014, 82(1), 147-160; https://doi.org/10.3797/scipharm.1310-18 - 18 Jan 2014

Cited by 17 | Viewed by 1566

Abstract

Two new eudesmane derivatives (3 and 8) were isolated from the ethanol extract of the aerial parts of Kaunia lasiophthalma Griseb, together with 14 known eudesmane, germacrane, and guaiane sesquiterpenes, and four flavones. The structures and relative configurations of all the [...] Read more.

Two new eudesmane derivatives (3 and 8) were isolated from the ethanol extract of the aerial parts of Kaunia lasiophthalma Griseb, together with 14 known eudesmane, germacrane, and guaiane sesquiterpenes, and four flavones. The structures and relative configurations of all the compounds were established by NMR spectroscopy and high-resolution mass spectrometry. The anticancer activity of sesquiterpenes 1, 3, 6–9, 11, 12, 14, and 16 was evaluated in vitro with the breast cancer cell lines HCC1937, JIMT-1, L56Br-C1, MCF-7, and SK-BR-3, and compared with the cytotoxicity in the non-cancerous breast epithelial cell line MCF-10A. All compounds were found to possess anticancer activity, and compound 1 was the most potent in all of the investigated cancer cell lines with IC50 values ranging between 2.0 and 6.2 μM. In order to demonstrate the importance of the α-methylene-γ-lactone/ester moiety present in all compounds for the effects on the cells, the methyl cysteine adduct 21 was prepared from 9 and found to be inactive or considerably less potent. Full article

673 KiB

Open AccessArticle

Dissolution Improvement of Atorvastatin Calcium using Modified Locust Bean Gum by the Solid Dispersion Technique

by Dharmila PANGHAL, Manju NAGPAL, Gurjeet Singh THAKUR and Sandeep ARORA

Sci. Pharm. 2014, 82(1), 177-192; https://doi.org/10.3797/scipharm.1301-23 - 9 Dec 2013

Cited by 29 | Viewed by 2001

Abstract

The present research was aimed at the enhancement of the dissolution rate of atorvastatin calcium by the solid dispersion technique using modified locust bean gum. Solid dispersions (SD) using modified locust bean gum were prepared by the modified solvent evaporation method. Other mixtures [...] Read more.

The present research was aimed at the enhancement of the dissolution rate of atorvastatin calcium by the solid dispersion technique using modified locust bean gum. Solid dispersions (SD) using modified locust bean gum were prepared by the modified solvent evaporation method. Other mixtures were also prepared by physical mixing, co-grinding, and the kneading method. The locust bean gum was subjected to heat for modification. The prepared solid dispersions and other mixtures were evaluated for equilibrium solubility studies, content uniformity, FTIR, DSC, XRD, in vitro drug release, and in vivo pharmacodynamic studies. The equilibrium solubility was enhanced in the solid dispersions (in a drug:polymer ratio of 1:6) and other mixtures such as the co-grinding mixture (CGM) and kneading mixture (KM). Maximum dissolution rate was observed in the solid dispersion batch SD3 (i.e. 50% within 15 min) with maximum drug release after 2 h (80%) out of all solid dispersions. The co-grinding mixture also exhibited a significant enhancement in the dissolution rate among the other mixtures. FTIR studies revealed the absence of drug-polymer interaction in the solid dispersions. Minor shifts in the endothermic peaks of the DSC thermograms of SD3 and CGM indicated slight changes in drug crystallinity. XRD studies further confirmed the results of DSC and FTIR. Topological changes were observed in SEM images of SD3 and CGM. In vivo pharmacodynamic studies indicated an improved efficacy of the optimized batch SD3 as compared to the pure drug at a dose of 3 mg/kg/day. Modified locust bean gum can be a promising carrier for solubility enhancement of poorly water-soluble drugs. The lower viscosity and wetting ability of MLBG, reduction in particle size, and decreased crystallinity of the drug are responsible for the dissolution enhancement of atorvastatin. The co-grinding mixture can be a good alternative to solid dispersions prepared by modified solvent evaporation due to its ease of preparation and significant improvement in dissolution characteristics. Full article

420 KiB

Open AccessArticle

QSAR and Molecular Docking Studies of Oxadiazole-Ligated Pyrrole Derivatives as Enoyl-ACP (CoA) Reductase Inhibitors

by Kalyani D. ASGAONKAR, Ganesh D. MOTE and Trupti S. CHITRE

Sci. Pharm. 2014, 82(1), 71-86; https://doi.org/10.3797/scipharm.1310-05 - 24 Nov 2013

Cited by 19 | Viewed by 1801

Abstract

A quantitative structure-activity relationship model was developed on a series of compounds containing oxadiazole-ligated pyrrole pharmacophore to identify key structural fragments required for anti-tubercular activity. Two-dimensional (2D) and three-dimensional (3D) QSAR studies were performed using multiple linear regression (MLR) analysis and k-nearest neighbour [...] Read more.

A quantitative structure-activity relationship model was developed on a series of compounds containing oxadiazole-ligated pyrrole pharmacophore to identify key structural fragments required for anti-tubercular activity. Two-dimensional (2D) and three-dimensional (3D) QSAR studies were performed using multiple linear regression (MLR) analysis and k-nearest neighbour molecular field analysis (kNN-MFA), respectively. The developed QSAR models were found to be statistically significant with respect to training, cross-validation, and external validation. New chemical entities (NCEs) were designed based on the results of the 2D- and 3D-QSAR. NCEs were subjected to Lipinski’s screen to ensure the drug-like pharmacokinetic profile of the designed compounds in order to improve their bioavailability. Also, the binding ability of the NCEs with enoyl-ACP (CoA) reductase was assessed by docking. Full article

136 KiB

Open AccessShort Communication

HPLC Analysis and Cytotoxicity of n-Butanol Extract from Glyphaea brevis Roots Against C6 Glioma Cells

by Koffi Marcel KONAN, Janat Akhanovna MAMYRBEKOVA-BEKRO, Norbert BAKALARA, David VIRIEUX, Jean-Luc PIRAT and Yves-Alain BEKRO

Sci. Pharm. 2014, 82(1), 171-176; https://doi.org/10.3797/scipharm.1307-08 - 19 Nov 2013

Cited by 7 | Viewed by 1396

Abstract

The n-butanol extract of the roots of Glyphaea brevis was analysed. HPLC analysis suggested the presence of phenolic compounds like protocatechuic acid (PCA). The extract showed moderate cytotoxic activity against C6 glioma cells (EC50 > 1 mg/ml). Full article

283 KiB

Open AccessArticle

Development and Validation of a Gas Chromatography Method for the Trace Level Determination of Allylamine in Sevelamer Hydrochloride and Sevelamer Carbonate Drug Substances

by Raju V. S. N. KADIYALA, Pavan Kumar S. R. KOTHAPALLI, Madhava Reddy PEDDOLLA, Pradeep RAJPUT, Hemant Kumar SHARMA, Shankar Reddy BUDETI, Himabindu GANDHAM and Annapurna NOWDURI

Sci. Pharm. 2014, 82(1), 117-128; https://doi.org/10.3797/scipharm.1309-12 - 14 Nov 2013

Cited by 2 | Viewed by 2174

Abstract

A capillary gas chromatography method using a flame ionization detector has been developed for the trace analysis of allylamine (AA) in sevelamer hydrochloride (SVH) and sevelamer carbonate (SVC) drug substances. The method utilized a mega bore capillary column DB-CAM (30 m x 0.53 [...] Read more.

A capillary gas chromatography method using a flame ionization detector has been developed for the trace analysis of allylamine (AA) in sevelamer hydrochloride (SVH) and sevelamer carbonate (SVC) drug substances. The method utilized a mega bore capillary column DB-CAM (30 m x 0.53 mm x 1.0 μm) with a bonded and cross-linked, base-deactivated polyethylene glycol stationary phase and was validated for specificity, sensitivity, precision, linearity, and accuracy. The detection and quantitation limits obtained for allylamine were 2 μg/g and 6 μg/g, respectively. The method was found to be linear in the range between 6 μg/g and 148 μg/g with a correlation coefficient of 0.9990. The average recoveries obtained in SVH and SVC were 93.9% and 99.1%, respectively. The developed method was found to be robust for the determination of AA in sevelamer drug substances and also the specificity was demonstrated with a gas chromatograph coupled with a mass spectrometer. Full article

204 KiB

Open AccessArticle

Increased 5-HT Levels Following Repeated Administration of Nigella sativa L. (Black Seed) Oil Produce Antidepressant Effects in Rats

by Tahira PERVEEN, Saida HAIDER, Nudrat Anwar ZUBERI, Sadia SALEEM, Sana SADAF and Zehra BATOOL

Sci. Pharm. 2014, 82(1), 161-170; https://doi.org/10.3797/scipharm.1304-19 - 5 Nov 2013

Cited by 40 | Viewed by 4126

Abstract

The seeds of Nigella sativa L., commonly known as black seed or black cumin, and its extracts are used in folk medicine in the Middle East and in Asian countries for the promotion of good health and as a remedy for many ailments. [...] Read more.

The seeds of Nigella sativa L., commonly known as black seed or black cumin, and its extracts are used in folk medicine in the Middle East and in Asian countries for the promotion of good health and as a remedy for many ailments. These seeds have many acclaimed medicinal properties such as broncho-dilatory, immunopotentiating, analgesic, anti-inflammatory, and hypotensive. In the present study, the antidepressant activity following the repeated administration of Nigella sativa L. oil has been monitored using the forced swim test. Rats treated with Nigella sativa L. oil exhibited a significant increase in struggling time after oral administration of Nigella sativa L. oil (0.1 ml/kg/day) for four weeks. Nigella sativa L. oil increased brain 5-HT levels and decreased 5-HT turnover (5-HT/5-HIAA ratio). Levels of tryptophan increased significantly in the brain and plasma following the repeated administration of Nigella sativa L. oil. Nigella sativa L. oil showed a potential antidepressant-like effect. Full article

250 KiB

Open AccessArticle

Development and Validation of a Stability-Indicating RP-HPLC Method for the Estimation of Drotaverine Impurities in API and Pharmaceutical Formulation

by Veera Raghava Raju THUMMALA, Satya Sankarsana Jagan Mohan THARLAPU, Vijay Kumar REKULAPALLI, Mrutyunjaya Rao IVATURI and Someswara Rao NITTALA

Sci. Pharm. 2014, 82(1), 99-116; https://doi.org/10.3797/scipharm.1309-06 - 21 Oct 2013

Viewed by 2819

Abstract

A sensitive, stability-indicating gradient RP-HPLC method with PDA detection has been developed for the simultaneous analysis of drotaverine impurities in active pharmaceutical ingredient (API) and pharmaceutical formulations. Efficient chromatographic separation was achieved on an XTerra RP18, 150 × 4.6 mm, 5 μm column [...] Read more.

A sensitive, stability-indicating gradient RP-HPLC method with PDA detection has been developed for the simultaneous analysis of drotaverine impurities in active pharmaceutical ingredient (API) and pharmaceutical formulations. Efficient chromatographic separation was achieved on an XTerra RP18, 150 × 4.6 mm, 5 μm column using gradient elution at 230 nm detection wavelength. The optimized mobile phase consisted of a 0.02 M potassium dihydrogen ortho-phosphate buffer of pH 3.0 as solvent A and acetonitrile as solvent B. The flow rate of the mobile phase was 1.0 mL min⁻¹ with a column temperature of 25°C. The method showed linearity over the range of 0.251–10.033 μg/mL, 0.231–9.995 μg/mL, 0.230–10.089 μg/mL, 0.334–10.011 μg/mL, and 0.324–10.050 μg/mL for impurities 1, 2, 3, 4, and drotaverine, respectively, with a correlation coefficient greater than 0.999. The relative retention times and relative response factors of impurities 1, 2, 3, 4 were 0.36, 0.90, 1.42, 1.55 and 1.04, 0.84, 1.10, 1.30, respectively. The drotaverine formulation sample was subjected to the stress conditions of acid, base, oxidative, thermal, humidity, and photolytic degradation. Drotaverine was found to degrade significantly in peroxide, base, and heat stress conditions. The degradation products were well-resolved from drotaverine and its impurities. The peak purity test results confirmed that the drotaverine peak was homogenous and pure in all stress samples and the mass balance was found to be more than 98%, thus proving the stability-indicating power of the method. The developed method was validated according to ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision, and robustness. Full article

1261 KiB

Open AccessArticle

Isolation and Evaluation of the Enantiospecific Antitubercular Activity of a Novel Triazole Compound

by Radha SHEKAR, Barij Nayan SINHA, Arindam MUKHOPADHYA and Mariam S. DEGANI

Sci. Pharm. 2014, 82(1), 87-98; https://doi.org/10.3797/scipharm.1308-15 - 21 Oct 2013

Cited by 2 | Viewed by 1273

Abstract

Cyclohex-3-enyl(5-phenyl-4H-1,2,4-triazol-3-yl)methanol (MSDRT 12) is a novel triazole-based antitubercular compound with two chiral centers. To evaluate the enantiospecific antitubercular activity, the four stereoisomers were isolated using preparative chiral chromatography and the individual stereoisomers were evaluated using the resazurin microtiter assay method (REMA) [...] Read more.

Cyclohex-3-enyl(5-phenyl-4H-1,2,4-triazol-3-yl)methanol (MSDRT 12) is a novel triazole-based antitubercular compound with two chiral centers. To evaluate the enantiospecific antitubercular activity, the four stereoisomers were isolated using preparative chiral chromatography and the individual stereoisomers were evaluated using the resazurin microtiter assay method (REMA) and a microbroth dilution technique against the Mycobacterium tuberculosis H37Rv strain. Isomer III of MSDRT 12 was found to be the most potent with a minimum inhibitory concentration (MIC) of 0.78 μg/mL, Isomer II had a MIC of 12.5 μg/mL, and isomers I and IV showed no activity. The diastereomeric mixture of MSDRT 12 showed a MIC of 3.125 μg/mL and isoniazid, used as the standard drug, showed a MIC of 0.4 μg/mL. This confirms the necessity of screening individual enantiomers for their pharmacological activity early in the discovery phase to identify the most potent isomer for further development efforts. Full article

317 KiB

Open AccessArticle

Regioselective Synthesis, Characterization, and Antimicrobial Activities of Some New Monosaccharide Derivatives

by Sarkar M. A. KAWSAR, Md O. FARUK, Mohammad S. RAHMAN, Yuki FUJII and Yasuhiro OZEKI

Sci. Pharm. 2014, 82(1), 1-20; https://doi.org/10.3797/scipharm.1308-03 - 26 Sep 2013

Cited by 31 | Viewed by 1803

Abstract

A regioselective acylation series of methyl α-D-glucopyranoside (1), methyl 3-O-benzoyl-4,6-O-benzylidene-α-D-mannopyranoside (1A), and methyl 4,6-O-benzylidene-2-O-(3,5-dinitrobenzoyl)-α-D-mannopyranoside (1B) has been carried out by the direct acylation method and afforded the 2,6-di-O [...] Read more.

A regioselective acylation series of methyl α-D-glucopyranoside (1), methyl 3-O-benzoyl-4,6-O-benzylidene-α-D-mannopyranoside (1A), and methyl 4,6-O-benzylidene-2-O-(3,5-dinitrobenzoyl)-α-D-mannopyranoside (1B) has been carried out by the direct acylation method and afforded the 2,6-di-O-glucopyranoside and 2 or 3-O-mannopyranoside derivatives in an excellent yield. In order to obtain newer products, the 2,6-di-O-glucopyranoside derivative was further transformed to a series of 3,4-di-O-acyl derivatives containing a wide variety of functionalities in a single molecular framework. The structures of the newly synthesized compounds were elucidated on the basis of IR, 1H-NMR, 13C-NMR, 13C-DEPT spectral data, and elemental analysis. These synthesized derivatives were screened for in vitro antimicrobial activities against ten human pathogenic and five phytopathogenic microorganisms. A number of test compounds showed remarkable antimicrobial activity comparable to, and in some cases even higher than, the standard antibiotics employed. It was observed that methyl 3,4-di-O-(3-chlorobenzoyl)-2,6-di-O-hexanoyl-α-D-glucopyranoside (8) ex-hibited a varied range of MIC from 12.5 μg/disc to 25 μg/disc by the disk diffusion method and 1000 μg/mL to 1250 μg/mL by the broth macrodilution method. Full article

240 KiB

Open AccessArticle

Evaluation of Serum Levels of HER2, MMP-9, Nitric Oxide, and Total Antioxidant Capacity in Egyptian Breast Cancer Patients: Correlation with Clinico-Pathological Parameters

by Yara A. RASHAD, Tawfik R. ELKHODARY, Amal M. EL-GAYAR and Laila A. EISSA

Sci. Pharm. 2014, 82(1), 129-146; https://doi.org/10.3797/scipharm.1306-18 - 22 Sep 2013

Cited by 23 | Viewed by 1773

Abstract

Breast cancer is by far the most common cancer in women worldwide and the main cause of cancer-related mortality. Breast cancer accounts for 38% of all malignancies among Egyptian women. The aim of our study was to evaluate the serum levels of human [...] Read more.

Breast cancer is by far the most common cancer in women worldwide and the main cause of cancer-related mortality. Breast cancer accounts for 38% of all malignancies among Egyptian women. The aim of our study was to evaluate the serum levels of human epidermal growth factor receptor-2 (HER2), matrix metalloproteinase-9 (MMP-9), nitric oxide (NO), and total antioxidant capacity (TAC) in breast cancer patients and to correlate these markers with clinico-pathological parameters. Serum HER2, MMP-9, and carcinoma antigen 15-3 (CA 15-3) were assessed in 80 breast cancer patients and ten healthy subjects as a control group by the enzyme-linked immunosorbent assay (ELISA) technique while NO and TAC were assessed by a colorimetric method. Serum HER2 was ≥15 ng/mL in nine patients (11.3%). High HER2 ECD levels were significantly associated with tissue HER2 (P<0.0001), metastasis (P= 0.0024), and negativity of both estrogen (P=0.0075) and progesterone (P=0.0239) receptors. Serum MMP-9 (P=0.0013), NO (P<0.0001), and CA 15-3 (P<0.0001) were significantly increased while serum TAC was significantly (P=0.01) decreased in breast cancer patients as compared to the control group. Serum MMP-9 was increased significantly (P=0.028) in metastatic patients as compared to non-metastatic patients. We found a positive correlation between serum HER2 and CA 15-3 (r=36, p=0.005). In conclusion, serum HER2 reflects the tissue HER2 status of breast cancer, so the determination of serum HER2 is helpful in assessing HER2 status, but in addition, a high level may reflect metastatic disease. Also, serum MMP-9 can be useful for denoting the development of metastasis in breast cancer patients. Follow-up is needed to evaluate the value of serum HER2 and MMP-9 as prognostic markers. Full article

317 KiB

Open AccessArticle

Prediction of Pharmacokinetic Parameters Using a Genetic Algorithm Combined with an Artificial Neural Network for a Series of Alkaloid Drugs

by Majid ZANDKARIMI, Mohammad SHAFIEI, Farzin HADIZADEH, Mohammad Ali DARBANDI and Kaveh TABRIZIAN

Sci. Pharm. 2014, 82(1), 53-70; https://doi.org/10.3797/scipharm.1306-10 - 22 Sep 2013

Cited by 6 | Viewed by 1833

Abstract

An important goal for drug development within the pharmaceutical industry is the application of simple methods to determine human pharmacokinetic parameters. Effective computing tools are able to increase scientists’ ability to make precise selections of chemical compounds in accordance with desired pharmacokinetic and [...] Read more.

An important goal for drug development within the pharmaceutical industry is the application of simple methods to determine human pharmacokinetic parameters. Effective computing tools are able to increase scientists’ ability to make precise selections of chemical compounds in accordance with desired pharmacokinetic and safety profiles. This work presents a method for making predictions of the clearance, plasma protein binding, and volume of distribution for alkaloid drugs. The tools used in this method were genetic algorithms (GAs) combined with artificial neural networks (ANNs) and these were applied to select the most relevant molecular descriptors and to develop quantitative structure-pharmacokinetic relationship (QSPkR) models. Results showed that three-dimensional structural descriptors had more influence on QSPkR models. The models developed in this study were able to predict systemic clearance, volume of distribution, and plasma protein binding with normalized root mean square error (NRMSE) values of 0.151, 0.263, and 0.423, respectively. These results demonstrate an acceptable level of efficiency of the developed models for the prediction of pharmacokinetic parameters. Full article

121 KiB

Open AccessShort Communication

Biological Evaluation of Isoniazid Derivatives as an Anticancer Class

by Felipe A. R. RODRIGUES, Augusto C. A. OLIVEIRA, Bruno C. CAVALCANTI, Claudia PESSOA, Alessandra C. PINHEIRO and Marcus V. N. DE SOUZA

Sci. Pharm. 2014, 82(1), 21-28; https://doi.org/10.3797/scipharm.1307-25 - 22 Sep 2013

Cited by 41 | Viewed by 2012

Abstract

A series of thirty-two isoniazid derivatives have been evaluated for their activity against four human cancer cell lines with potent cytotoxicity (IC50 ranging from 0.61 to 3.36 μg/mL). The structure-activity relationship (SAR) analysis indicated the number, the positions, and the types of substituents [...] Read more.

A series of thirty-two isoniazid derivatives have been evaluated for their activity against four human cancer cell lines with potent cytotoxicity (IC50 ranging from 0.61 to 3.36 μg/mL). The structure-activity relationship (SAR) analysis indicated the number, the positions, and the types of substituents attached to the aromatic ring as being critical factors for the biological activity. Briefly, we observed that the presence of a hydroxyl group on the benzene ring plays an important role in the anticancer activity of this series, especially when it is located in ortho-position. Among the thirty-two compounds, three displayed good cytotoxic activity when compared to the reference drug doxorubicin and are thus being considered leading compounds of this new class. Full article

519 KiB

Open AccessArticle

Synthesis and Evaluation of [⁶⁷Ga]-AMD3100: A Novel Imaging Agent for Targeting the Chemokine Receptor CXCR4

by Ayuob AGHANEJAD, Amir R. JALILIAN, Yousef FAZAELI, Behrouz ALIREZAPOOR, Mehraban POULADI, Davoud BEIKI, Stephan MAUS and Ali KHALAJ

Sci. Pharm. 2014, 82(1), 29-42; https://doi.org/10.3797/scipharm.1305-18 - 12 Sep 2013

Cited by 39 | Viewed by 2118

Abstract

In order to develop a possible C-X-C chemokine receptor type 4 (CXCR4) imaging agent for oncological scintigraphy, [67Ga]-labeled 1,1′-[1,4-Phenylene-bis(methylene)]bis(1,4,8,11-tetraazacyclotetradecane) ([⁶⁷Ga]-AMD3100) was prepared by using [⁶⁷Ga]GaCl₃ and AMD-3100 for 2 h at 50 °C (radiochemical purity: >95% ITLC, >99% [...] Read more.

In order to develop a possible C-X-C chemokine receptor type 4 (CXCR4) imaging agent for oncological scintigraphy, [67Ga]-labeled 1,1′-[1,4-Phenylene-bis(methylene)]bis(1,4,8,11-tetraazacyclotetradecane) ([⁶⁷Ga]-AMD3100) was prepared by using [⁶⁷Ga]GaCl₃ and AMD-3100 for 2 h at 50 °C (radiochemical purity: >95% ITLC, >99% HPLC, specific activity: 1800–2000 TBq/mmol) in acetate buffer. The stability of the complex was checked in the presence of human serum (37 °C) and in the final formulation for four days. The biodistribution of the labeled compound in the vital organs of wild type Sprague-Dawley rats was determined and compared with that of the free Ga³⁺ cation up to 48 h. Considering the spleen as the target organ, the best target:non target ratios were obtained 48 h post-injection (spleen:blood ratio; 14.5 and spleen:muscle ratio; 88.4). Initial SPECT images and biodistribution results in the wild type rats matched each other and demonstrated rapid washout of the tracer from the urinary tract. SPECT images in human breast carcinoma-bearing mice demonstrated a detectable tumor uptake in 48 h post-injection. Full article

535 KiB

Open AccessArticle

Isolation, Identification, and Characterization of an Unknown Impurity in Lovastatin EP

by Chandrakant BELWAL, Praveen Kumar GOYAL, Anup BALTE, Sandeep KOLHE, Kamlesh CHAUHAN, Ajay Singh RAWAT and Anand VARDHAN

Sci. Pharm. 2014, 82(1), 43-52; https://doi.org/10.3797/scipharm.1305-04 - 1 Jul 2013

Cited by 11 | Viewed by 1745

Abstract

An unknown impurity in the fermentation-based drug substance lovastatin at 0.52 RRT was observed invariably in all batches when analyzed by HPLC as per the PhEur monograph. This impurity was isolated from the impurity-enriched sample using reversed-phase preparative HPLC and characterized by using [...] Read more.

An unknown impurity in the fermentation-based drug substance lovastatin at 0.52 RRT was observed invariably in all batches when analyzed by HPLC as per the PhEur monograph. This impurity was isolated from the impurity-enriched sample using reversed-phase preparative HPLC and characterized by using spectroscopic (PMR, CMR, MASS, and UV) techniques as the structurally-related compound Monacolin-X, having the molecular formula C₂₄H₃₄O₆ and the chemical name 2-methyl-3-oxobutanoic acid 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester. Full article

Journal Menu

Journal Browser

Sci. Pharm., Volume 82, Issue 1 (March 2014) – 16 articles , Pages 1-220

Further Information

Guidelines

MDPI Initiatives

Follow MDPI