Scientia Pharmaceutica

301 KiB

Open AccessIntroduction

Instructions for Authors 2008

by Scientia Pharmaceutica

Sci. Pharm. 2008, 76(2), 321-332; https://doi.org/10.3797/scipharm.aut-08-02 - 31 May 2008

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Effects of Ethanol or Naltrexone after Ethanol Exposure on Plasma Levels of Hepatic Enzymes, Lipid Profile and Apolipoprotein in Rats

by Silvânia M. M. VASCONCELOS, Paula M. SOARES, Natália M. LIMA, Roberto F. PEREIRA, Renata S. ALVES, Maria Gorette R. QUEIROZ, Danielle S. MACEDO, Rivelilson M. FREITAS, Francisca Cléa F. SOUSA, Marta Maria F. FONTELES and Glauce S. Barros VIANA

Sci. Pharm. 2008, 76(2), 305-320; https://doi.org/10.3797/scipharm.0804-02 - 31 May 2008

Viewed by 1007

Abstract

This work studied the effects of ethanol and naltrexone on plasma levels of hepatic enzymes, lipid profiles and apoprotein (APO-A1). Rats were treated daily with ethanol for 7 days and, after ethanol discontinuation, they received naltrexone up to the 14th day. The results [...] Read more.

This work studied the effects of ethanol and naltrexone on plasma levels of hepatic enzymes, lipid profiles and apoprotein (APO-A1). Rats were treated daily with ethanol for 7 days and, after ethanol discontinuation, they received naltrexone up to the 14th day. The results showed increased alanine aminotransferase (ALT) and aspartate aminotranferase (AST) activities, as well as total cholesterol (TC), triglycerides (TGI) and high density lipoprotein cholesterol (HDL-C) levels after ethanol. Naltrexone alone significantly increased APO-A1 and TGI levels and significantly decreased TC concentrations. Naltrexone treatment after ethanol exposure leads to a significant increase in both ALT (48%) and AST (34%). While no changes were seen in HDL-C levels, naltrexone blocked the increase in TC levels induced by ethanol. However, TGI as well as APO-A1 levels were maintained at higher values as compared to controls and similar to those observed to the naltrexone group without ethanol treatment. The work indicates that the hypolipaemic effect of naltrexone after ethanol exposure is a favorable point to the use of this opioid antagonist in the treatment of alcoholism. Full article

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Open AccessArticle

Solution Phase Combinatorial Synthesis and Screening of Mini Libraries of Arylchalcones for Antibacterial Activity

by Neela M. BHATIA and Kakasaheb MAHADIK

Sci. Pharm. 2008, 76(2), 259-268; https://doi.org/10.3797/scipharm.0803-36 - 28 May 2008

Cited by 7 | Viewed by 1036

Abstract

The solution-phase combinatorial synthesis of aryl chalcones was studied by synthesizing a 6x4 array mini library. The mini libraries of chalcones were synthesized by condensation of 4-substituted acetophenones and various aryl/heteroaryl carbaldehydes. All the synthesized mini libraries were screened for antibacterial activity using [...] Read more.

The solution-phase combinatorial synthesis of aryl chalcones was studied by synthesizing a 6x4 array mini library. The mini libraries of chalcones were synthesized by condensation of 4-substituted acetophenones and various aryl/heteroaryl carbaldehydes. All the synthesized mini libraries were screened for antibacterial activity using serial dilution method. The mini-libraries 3{1a,2a–d}, 3{1b,2a–d}, 3{1a–f,2a} and 3{1a–f,2c}were found to be most active of the synthesized mini libraries. The common elements present in the identified pool of interest were used to individually synthesize four compounds which were individually subjected to antibacterial activity evaluation. The compound 3-(4-chlorophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one exhibited significant activity that was better than that of the other three compounds synthesized. The anti-bacterial activity of the identified hit was also found to be better than all mini-libraries, indicating utility of combinatorial synthesis and the assumption there in for lead identification. Full article

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Open AccessArticle

Preservative Evaluation of Novel 2,4-Hexadienoic Acid Derivatives in Aluminium Hydroxide Gel – USP

by Vikramjeet JUDGE, Balasubramanian NARASIMHAN, Rakesh NARANG, Ruchita OHLAN and Sucheta OHLAN

Sci. Pharm. 2008, 76(2), 269-278; https://doi.org/10.3797/scipharm.0803-14 - 22 May 2008

Cited by 3 | Viewed by 1053

Abstract

The potential derivatives of sorbic acid (2,4-hexadienoic acid) from our previous study were subjected to preservative efficacy testing. Aluminium Hydroxide Gel – USP was used as a pharmaceutical product and Staphylococcus aureus MTCC 2901, Bacillus subtilis MTCC 2063, Escherichia coli MTCC [...] Read more.

The potential derivatives of sorbic acid (2,4-hexadienoic acid) from our previous study were subjected to preservative efficacy testing. Aluminium Hydroxide Gel – USP was used as a pharmaceutical product and Staphylococcus aureus MTCC 2901, Bacillus subtilis MTCC 2063, Escherichia coli MTCC 1652, Candida albicans MTCC 227 and Aspergillus niger MTCC 8189 were used as representative challenging microorganisms for antimicrobial effectiveness testing as per USP 2004. The hexadienoic acid derivative, m-nitrosorbanilide has better preservative efficacy than sorbic acid as well as the standard preservatives, methyl paraben and propyl paraben. Full article

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Open AccessArticle

Rosiglitazone modifies PEDF gene expression and protein levels in the Koletsky rat choroid-RPE complex

by Jena J. STEINLE, Bethany L. LASHBROOK and William J. BANZ

Sci. Pharm. 2008, 76(2), 133-150; https://doi.org/10.3797/scipharm.0803-29 - 21 May 2008

Viewed by 922

Abstract

The purpose of this study was to determine whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)γ ligand, altered growth factor expression in the choroid-RPE complex of Koletsky rats. Using lean and obese Koletsky rats fed a normal or rosiglitazone-supplemented diet, gene and protein expression [...] Read more.

The purpose of this study was to determine whether rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)γ ligand, altered growth factor expression in the choroid-RPE complex of Koletsky rats. Using lean and obese Koletsky rats fed a normal or rosiglitazone-supplemented diet, gene and protein expression of vascular endothelial growth factor (VEGF), pigment epithelial derived growth factor (PEDF), angiopoietin 1, and its receptor, Tie-2, were assessed. Both gene expression and protein expression of PEDF were significantly increased in both obese and lean Koletsky rats treated with rosiglitazone diet. Gene expression of VEGF, angiopoietin-1 and Tie-2 were increased after rosiglitazone treatment, without changes in protein expression. Since PPARγ ligands have been implicated in vascular remodeling, these results suggest that upregulation of PEDF expression may be a potential mechanism in the rat choroid-RPE complex. Full article

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Open AccessArticle

Antimicrobial Activities of some Synthesized Pyridines, Oxazines and Thiazoles from 3-Aryl-1-(2-naphthyl)prop-2-en-1-ones

by Salwa F. MOHAMED, Mohamed M. YOUSSEF, Abd El-Galil E. AMR and Eman R. KOTB

Sci. Pharm. 2008, 76(2), 279-304; https://doi.org/10.3797/scipharm.0804-09 - 19 May 2008

Cited by 47 | Viewed by 1500

Abstract

3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were reacted with ethyl cyanoacetate to produce 4-aryl-6-(2-naphthyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles, which were treated with ethyl chloroacetate to give the corresponding ester. Treatment of the latter ester with hydrazine hydrate or anthranilic acid afforded hydrazides and benzoxazines. The hydrazides were reacted with benzaldehyde or phenylisothiocyanate [...] Read more.

3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were reacted with ethyl cyanoacetate to produce 4-aryl-6-(2-naphthyl)-2-oxo-1,2-dihydropyridine-3-carbonitriles, which were treated with ethyl chloroacetate to give the corresponding ester. Treatment of the latter ester with hydrazine hydrate or anthranilic acid afforded hydrazides and benzoxazines. The hydrazides were reacted with benzaldehyde or phenylisothiocyanate to afford the corresponding hydrazone and thiosemicarbazide derivatives, which were cyclized with chloroacetic acid or thioglycolic acid to the corresponding thiazole derivatives. 3-Aryl-1-(2-naphthyl)-prop-2-en-1-ones were either condensed with malononitrile under different conditions to produce carbonitrile derivatives or treated with active methylene reagents to afford the substituted cyclohexene derivatives. The structure assignment of the new compounds is based on chemical and spectroscopic evidence. Some of these compounds exhibited antimicrobial activities comparable to Ampicillin^® as reference drug. Full article

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Open AccessArticle

Preparation, Quality Control and Biodistribution Studies of two [¹¹¹In]-Rituximab Immunoconjugates

by Amir R. JALILIAN, Darush SARDARI, Leila KIA, Pejman ROWSHANFARZAD, Javad GAROUSI, Mehdi AKHLAGHI, Saeed SHANEHSAZZADEH and Mohammad MIRZAII

Sci. Pharm. 2008, 76(2), 151-170; https://doi.org/10.3797/scipharm.0804-07 - 18 May 2008

Cited by 19 | Viewed by 1805

Abstract

In order to use Auger-electron therapeutic effects in CD20 antigen targeting in lymphomas, Mabthera™ (rituximab) was successively labeled with [¹¹¹In]-indium chloride (185 MBq) after conjugation with freshly prepared macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) and ccDTPA separately. Conjugated-Rituximab was [...] Read more.

In order to use Auger-electron therapeutic effects in CD20 antigen targeting in lymphomas, Mabthera™ (rituximab) was successively labeled with [¹¹¹In]-indium chloride (185 MBq) after conjugation with freshly prepared macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) and ccDTPA separately. Conjugated-Rituximab was obtained by the addition of 1 ml of a rituximab pharmaceutical solution (5 mg/ml, in phosphate buffer, pH=7.8) to a glass tube pre-coated with freshly prepared DOTA-NHS or ccDTPA (0.01-0.1 mg) at 25°C. Radiolabeling was performed at 37°C in 3h and room temperature for one hour for DOTA-conjugate and DTPA-conjugate respectively. HPLC showed an overall radiochemical purity of 97.5 and 95% for DOTA and DTPA-conjugates respectively (Specific activity =2800-5600 GBq/mM). The final isotonic ¹¹¹In-rituximab complexes were checked by gel electrophoresis for radiolysis. Preliminary biodistribution studies in normal rat model performed to determine radioimmunoconjugates distribution of up to 48h. Full article

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Open AccessArticle

Tirofiban Preserves Endothelial Junctions and Decreases Endothelin-1

by Jing-Lin ZHAO, Yue-Jin YANG, Wei-Dong PEI, Yu-Hua SUN, Mei ZHAI, Ya-Xin LIU and Run-Lin GAO

Sci. Pharm. 2008, 76(2), 171-184; https://doi.org/10.3797/scipharm.0803-21 - 11 May 2008

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Abstract

It has been verified that glycoprotein IIb/IIIa inhibitor tirofiban can attenuate myocardial no-reflow. Myocardial no-reflow has been associated with alterations in endothelial junctions. In addition, ET-1 is an important mechanism for myocardial no-reflow. However, the effect of tirofiban on endothelial junctions and Endothelin-1 [...] Read more.

It has been verified that glycoprotein IIb/IIIa inhibitor tirofiban can attenuate myocardial no-reflow. Myocardial no-reflow has been associated with alterations in endothelial junctions. In addition, ET-1 is an important mechanism for myocardial no-reflow. However, the effect of tirofiban on endothelial junctions and Endothelin-1 (ET-1) is unknown. Methods: Twenty-eight mini-swines were randomized into 3 study groups: 10 in control, 10 given an intravenous infusion of tirofiban and 8 in sham-operated. Acute myocardial infarction and reperfusion model was created with three-hour occlusion of the left anterior descending coronary artery followed by one-hour reperfusion. Results: In control group, plasma ET-1 significantly increased, ET-1 or VE-cadherin level in the reflow and no-reflow myocardium was significantly higher or lower than that in normal myocardium. Compared with the control group, tirofiban significantly decreased plasma ET-1 and myocardial tissue ET-1, maintained VE-cadherin level. Conclusions: Tirofiban is effective in preserving endothelial junction. This beneficial effect of tirofiban could be partly due to its reduction of ET-1. Full article

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Open AccessReview

Chemical Structure Indices in In Silico Molecular Design

by Yenamandra S. PRABHAKAR and Manish K. GUPTA

Sci. Pharm. 2008, 76(2), 101-132; https://doi.org/10.3797/scipharm.0804-12 - 07 May 2008

Cited by 12 | Viewed by 1109

Abstract

The chemical structure indices have a significant role in providing direction to the design of chemotherapeutic agents. These indices come from the experimental domain as well as through the computations. While the experimental properties of compounds have practical value, the indices from computational [...] Read more.

The chemical structure indices have a significant role in providing direction to the design of chemotherapeutic agents. These indices come from the experimental domain as well as through the computations. While the experimental properties of compounds have practical value, the indices from computational domain offer fast and economic inputs to simulations. This review article discusses various methods and issues involved in the generation of physicochemical, quantum chemical, graph theoretical, chirality indices, flexible descriptors, molecular fingerprints and 3D chemical space descriptors etc for in silico molecular design approaches. A futuristic perspective of structural indices in drug design is outlined. Full article

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Open AccessArticle

Hepatoprotective and Antioxidant Effect of Pisonia aculeata L. against CCl₄-Induced Hepatic Damage in Rats

by Muthu Gounder PALANIVEL, Balasubramanian RAJKAPOOR, Raju SENTHIL KUMAR, John Wilking EINSTEIN, Ekambaram Prem KUMAR, Mani RUPESH KUMAR, Kunchu KAVITHA, Mohanraj PRADEEP KUMAR and Balasundaram JAYAKAR

Sci. Pharm. 2008, 76(2), 203-216; https://doi.org/10.3797/scipharm.0803-16 - 01 May 2008

Cited by 91 | Viewed by 2429

Abstract

Ethanol extract of Pisonia aculeata (EPA) was evaluated for hepatoprotective and antioxidant activities in rats. The plant extract (250 and 500 mg/kg, p.o.) showed a remarkable hepatoprotective and antioxidant activity against carbon tetrachloride (CCl₄)-induced hepatotoxicity as judged from the serum marker [...] Read more.

Ethanol extract of Pisonia aculeata (EPA) was evaluated for hepatoprotective and antioxidant activities in rats. The plant extract (250 and 500 mg/kg, p.o.) showed a remarkable hepatoprotective and antioxidant activity against carbon tetrachloride (CCl₄)-induced hepatotoxicity as judged from the serum marker enzymes and antioxidant levels in liver tissues. CCl₄-induced a significant rise in aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO) with a reduction of total protein, superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and glutathione S-transferase (GST). Treatment of rats with different doses of plant extract (250 and 500 mg/kg) significantly (P<0.001) altered serum marker enzymes and antioxidant levels to near normal against CCl₄-treated rats. The activity of the extract at dose of 500 mg/kg was comparable to the standard drug, silymarin (50 mg/kg, p.o.). Histopathological changes of liver sample were compared with respective control. Results indicate the hepatoprotective and antioxidant properties of P. aculeata against CCl₄-induced hepatotoxicity in rats. Full article

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Open AccessArticle

Catalytic Activity of Cytochrome P-450 using NADP⁺Reduced by an Anionic Hydride Organosiloxane

by Jessica E. MENDIETA-WEJEBE, José CORREA-BASURTO, Juan M. ACEVES, Daniel RAMÍREZ-ROSALES, José TRUJILLO-FERRARA, Rafael ZAMORANO-ULLOA and Martha C. ROSALES-HERNÁNDEZ

Sci. Pharm. 2008, 76(2), 241-258; https://doi.org/10.3797/scipharm.0803-01 - 21 Apr 2008

Cited by 2 | Viewed by 1038

Abstract

Abstract Cytochrome P-450 (P450) catalyzes a wide variety of chemical reactions; however, its use for in vitro assays has several limitations, the most striking one is the use of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) coenzyme. In this work, the P450 activity [...] Read more.

Abstract Cytochrome P-450 (P450) catalyzes a wide variety of chemical reactions; however, its use for in vitro assays has several limitations, the most striking one is the use of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) coenzyme. In this work, the P450 activity using NADP⁺ reduced by an anionic organosiloxane, commonly named silica hydride, was evaluated. The results showed that the reduction of NADP⁺with silica hydride was concentration- and time-dependent. P-450 activity was maintained when NADP⁺ and silica hydride were added during the reaction; however, it was lower than when commercial NADPH was employed. This is due to the ability of silica hydride to reduce P450 iron atom as corroborated by the electronic paramagnetic resonance (EPR). Furthermore, this compound possibly chelates FeII because, in its presence, the P450 affinity for aniline diminishes. However, the P450 activity was the best when NADP⁺ was reduced by silica hydride before the former was added to the reaction. Therefore, this system could be apt for studying biotransformation reactions. Full article

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Open AccessArticle

Synthesis and Pharmacological Evaluation of New 2-Substituted-5-{2-[(2-halobenzyl)thio)phenyl}-1,3,4-oxadiazoles as Anticonvulsant Agents

by Afshin ZARGHI, Samaneh HAMEDI, Fatemeh TOOTOONI, Behzad AMINI, Behrang SHARIFI, Mehrdad FAIZI, Seyed Abbas TABATABAI and Abbas SHAFIEE

Sci. Pharm. 2008, 76(2), 185-202; https://doi.org/10.3797/scipharm.0803-10 - 20 Apr 2008

Cited by 38 | Viewed by 1698

Abstract

A new series of 2-substituted-5-{2-[(2-halobenzyl)thio)phenyl}-1,3,4-oxadiazoles was designed, synthesized and investigated for anticonvulsant activities. The designed compounds contain the main essential pharmacophore for binding to the benzodiazepine receptors. Conformational analysis and superimposition of energy minima conformers of designed molecules on estazolam, a known benzodiazepine [...] Read more.

A new series of 2-substituted-5-{2-[(2-halobenzyl)thio)phenyl}-1,3,4-oxadiazoles was designed, synthesized and investigated for anticonvulsant activities. The designed compounds contain the main essential pharmacophore for binding to the benzodiazepine receptors. Conformational analysis and superimposition of energy minima conformers of designed molecules on estazolam, a known benzodiazepine receptor agonist, revealed that the main characteristics of the proposed benzodiazepine pharmacophore were well matched. Electroshock and pentylenetetrazole-induced lethal convulsion tests showed that some of the synthesized compounds had significant anticonvulsant activity. The structure-activity relationship study of these compounds indicated that the introduction of an amino group at position 2 of 1,3,4-oxadiazole ring and a fluoro substituent at the ortho position of the benzylthio moiety had the best anticonvulsant activity. Anticonvulsant effects of active compounds were antagonized by flumazenil, a benzodiazepine antagonist, which establish the involvement of benzodiazepine receptors in these effects. Full article

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Open AccessArticle

Synthesis, Characterization and Antimicrobial Studies on Some Newer Imidazole Analogs

by Rajiv DAHIYA

Sci. Pharm. 2008, 76(2), 217-240; https://doi.org/10.3797/scipharm.0803-04 - 17 Apr 2008

Cited by 31 | Viewed by 1361

Abstract

A novel series of 3,5-diiodo-4-(2-methyl-1H-imidazol-5-yl)benzoic acid analogs of amino acids, dipeptides and tripeptides was synthesized by using dicyclohexylcarbodiimide and diisopropylcarbodiimide (DCC/DIPC) as coupling agents and triethylamine (TEA) as base. Structures of all the newly synthesized compounds were confirmed by elemental analysis [...] Read more.

A novel series of 3,5-diiodo-4-(2-methyl-1H-imidazol-5-yl)benzoic acid analogs of amino acids, dipeptides and tripeptides was synthesized by using dicyclohexylcarbodiimide and diisopropylcarbodiimide (DCC/DIPC) as coupling agents and triethylamine (TEA) as base. Structures of all the newly synthesized compounds were confirmed by elemental analysis and IR, ¹H NMR, ¹³C NMR and mass spectral data. Imidazolopeptides were investigated for their antimicrobial activity and some of newly synthesized compounds 2c, 2d, 2h and their hydrolyzed analogs 3b, 3d exhibited potent bioactivity against pathogenic fungi Candida albicans and dermatophytes Trichophyton mentagrophytes and Microsporum audouinii with MIC values of 12.5-6 μg/ml, as compared to the reference drug - griseofulvin. In addition, moderate activity against gram negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae was also observed for synthesized imidazolopeptides. Full article

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Sci. Pharm., Volume 76, Issue 2 (June 2008) – 13 articles , Pages 101-332

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