Showing papers in "Acta Pharmaceutica in 2004"

Anticonvulsant activity of Schiff bases of isatin derivatives.

Abstract: Schiff bases of N-methyl and N-acetyl isatin derivatives with different aryl amines have been synthesized and screened for anticonvulsant activities against maximal electroshock (MES) and subcutaneous metrazole (ScMet). N-methyl-5-bromo-3-(p-chlorophenylimino) isatin (2) exhibited anticonvulsant activity in MES and ScMet with LD50 > 600 mg kg(-1), showing better activity than the standard drugs phenytoin, carbamazepine and valproic acid. Thus, compound 2 may be chosen as a prototype for development of new anticonvulsants.

Quantitative analysis of the flavonoids in raw propolis from northern Croatia

Abstract: Spectrometric analyses of flavonoids in twenty propolis samples collected from ten different geographic localities in northern Croatia using two complementary methods, are reported. Flavones and flavonols were determined using aluminum chloride and expressed as quercetine equivalent while flavanones were determined using 2,4-dinitrophenylhydrazine and expressed as naringenin. Contents of flavones and flavonols were similar for most samples and ranged from 2 to 2.3%, except for one sample with a concentration of 1.3% and one sample in which it was not possible to detect flavones and flavonols. The content of flavanones in propolis samples is very variable. 55% of samples contain flavanons between 15 and 24% and 45% of samples between 4 and 14%. Total levels of flavonoids in raw propolis samples ranged between 5 and 26%; for the majority of samples (75%), the total level of flavonoids ranged between 15 and 25.9%. The high variability of flavanone concentration will affect biological activity of propolis preparations.

Antimicrobial activity of grapefruit seed and pulp ethanolic extract

Abstract: Antibacterial and antifungal activity of ethanolic extract of grapefruit (Citrus paradisi Macf., Rutaceae) seed and pulp was examined against 20 bacterial and 10 yeast strains. The level of antimicrobial effects was established using an in vitro agar assay and standard broth dilution susceptibility test. The contents of 3.92% of total polyphenols and 0.11% of flavonoids were determined spectrometrically in crude ethanolic extract. The presence of flavanones naringin and hesperidin in the extract was confirmed by TLC analysis. Ethanolic extract exibited the strongest antimicrobial effect against Salmonella enteritidis (MIC 2.06%, m/V). Other tested bacteria and yeasts were sensitive to extract concentrations ranging from 4.13% to 16.50% (m/V).

Healing potential of Anogeissus latifolia for dermal wounds in rats.

Abstract: Wound healing potential of ethanolic extract of Anogeissus latifolia bark (ALE) for treatment of dermal wounds in rats was studied on excision and incision wound models. HPTLC of the total extract was recorded for the purpose of standardization. Various parameters of incision wound, viz. epithelization period, scar area, tensile strength and hydroxyproline measurements along with wound contraction, were used to evaluate the effect of A. latifolia on wound healing. The results obtained indicate that A. latifolia accelerates the wound healing process by decreasing the surface area of the wound and increasing the tensile strength. Nitrofurazone ointment was used as a positive control. Complete epithelization was observed within 15 days with ALE. Measurements of the healed area and the hydroxyproline level were in agreement. Antibacterial activity of ALE was studied against Gram-positive (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae) compared to erythromycin and tetracycline. Moderate activity was observed against all organisms. The present study provides a scientific rationale for the traditional use of Anogeissus latifolia in the management of skin diseases such as sores, boils and itching.

The facts and controverses about selenium

Abstract: Selenium is a trace element, essential in small amounts, but it can be toxic in larger amounts. Levels in the body are mainly dependent on the amount of selenium in the diet, which is a function of the selenium content of the soil. Humans and animals require selenium for normal functioning of more than about 30 known selenoproteins, of which approximately 15 have been purified to allow characterisation of their biological functions. Selenopro- teins are comprised of four glutathione peroxidases, three iodothyronine deiodinases, three thioredoxin reductases, selenoprotein P, selenoprotein W and selenophosphate synthetase. Selenium is essential for normal functioning of the immune system and thyroid gland, making seleni- um an essential element for normal development, growth, metabolism, and defense of the body. Supportive func- tion of selenium in health and disease (male infertility, viral infections, including HIV, cancer, cardiovascular and autoimmune diseases) is documented in great number of clinical examinations. A great number of studies confirm that selenium supplementation plays a preventive and therapeutical role in different diseases. Definitive evidence regarding the preventive and therapeutical role of sele- nium as well as the exact mechanism of its action should be investigated in further studies. Investigations in Croatia indicate a possibility of inadequate selenium status of people in the area.

Synthesis and antimicrobial evaluation of naphtho[2,1-b]pyrano[2,3-d]pyrimidine and pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine derivatives.

Abstract: Several novel naphtho[2,1-b]pyrano[2,3-d]pyrimidines, pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines and their coumarin-3-yl derivatives were synthesized Some of these derivatives exhibited pronounced antimicrobial activities

Synthesis of some new annulated pyrazolo-pyrido (or pyrano) pyrimidine, pyrazolopyridine and pyranopyrazole derivatives.

Abstract: The bifunctional pyrazolopyridine (2) and pyrano-pyrazole (3) derivatives were prepared by the reaction of 2-(2,4-dinitrophenyl)-5-methyl-2,4-dihydro-3H-pyrazol-3-one (1) with p-methoxybenzaldehyde, malononitrile in the presence of ammonium acetate or piperidine, respectively. Compound 2 was used as the key intermediate to prepare the pyrazolo-pyrido-pyrimidine derivatives through its reaction with formic acid, formamide-formic acid-DMF, ammonium thiocyanate or reaction with triethyl orthoformate followed by cyclization with hydrazine hydrate. Reaction of 3 with triethyl orthoformate followed by cyclization with hydrazine hydrate gave the pyrazolo-pyrano-pyrimidine derivative 11. Reaction of ethyl-3-oxo-2-[2-phenyl-diazenyl]butanoate and ethyl 2-[2-(4-chlorophenyl)diazenyl]-3-oxobutanoate with 1 to give the pyrazolone derivatives 13a and 13b, was also considered.

Ethnomedical value of Cissampelos pareira extract in experimentally induced diarrhoea

Abstract: The antidiarrhoeal activity of the ethanolic extract of Cis- sampelos pareira (Menispermaceae) roots was assessed on experimental animals. The hydroethanolic extract (25- 100 mg dry extract kg -1 body mass, p.o.) exhibited a dose dependent decrease in the total number of faecal drop- pings (control 65, reduced to 26-46) and 29.2-60.0% inhi- bition in castor oil-induced diarrhoea. Further, C. pareira produced a significant (p < 0.01) and dose dependent re- duction in intestinal fluids accumulation (26.0-59.0%). The extract showed a greater inhibitory effect on the concentration of Na + (20.0 and 34.5%) than on the con- centration of K + (6.7 and 9.4%). The extract also reduced dose dependently the gastrointestinal transit from 46.4 and 38.7%, equivalent to 53.6 and 61.3%. However, C. pa- reira significantly reduced the lipid peroxidation and in- hibited the decrease in antioxidant enzyme levels (super- oxide dismutase and catalase) on prior administration to castor oil-induced fluid accumulation. The extract of C. pareira had no effect on normal defecation at 25 mg kg -1 in mice. However, 50 and 100 mg kg -1 inhibited defeca- tion by 100% in the initial 2 h and the activity was redu- ced to 40.0 and 73.0%, respectively, in the third hour.

Poly(lactide-co-glycolide) microparticles as systems for controlled release of proteins -- preparation and characterization.

Abstract: Poly(DL-lactide-co-glycolide) (PDLLGA) and poly(L-lactide-co-glycolide) (PLLGA) copolymers were prepared by bulk ring opening polymerization of lactide and glycolide and characterized by GPC, FTIR, 1H NMR and DSC. Copolymers with different molar masses at a constant lactide/glycolide ratio were used for preparation of bovine serum albumin (BSA)-loaded microparticles by the double emulsion w/o/w method. The influence of the copolymer molar mass and composition on the microparticle morphology, size, yield, degradation rate, BSA-loading efficiency and BSA release profile were studied. For microparticles prepared from PDLLGA copolymers, a biphasic profile for BSA release was found and for those made from PLLGA copolymers the release profile was typically triphasic; both of them were characterized by high initial burst release. Possible reasons for such behavior are discussed.

Synthesis and potential antimycotic activity of 4-substituted-3-(thiophene-2-yl-methyl)-Delta2-1,2,4-triazoline-5-thiones.

Abstract: In the reaction of hydrazide of thiophene-2-acetic acid (1) with isothiocyanates, the respective thiosemicarbazides 2a-g were obtained. Further cyclization with 2% NaOH led to formation of 4-substituted-3-(thiophene- 2-yl-methyl)-Delta2-1,2,4-triazoline-5-thiones (3a-g). These compounds showed promising antimycotic activity.

Qualitative and quantitative analysis of clopidogrel bisulphate polymorphs.

Abstract: This study deals with characterization and quantification of form I and form II of clopidogrel bisulphate (CLP), a selective and irreversible inhibitor of ADP-induced platelet aggregation. Thermal (DSC, TGA, HSM), crystallographic (XRD) and spectroscopic (FTIR) methods were used for characterization. After characterization of active pharmaceutical ingredient (API), these techniques were further used for identification of the polymorphic form present in three marketed formulations (tablets). FTIR method was successfully developed and validated for the quantification of form I in polymorph mixtures.

FT-IR and NMR spectroscopic studies of salicylic acid derivatives. II. Comparison of 2-hydroxy- and 2,4- and 2,5-dihydroxy derivatives.

Abstract: The 2,4- and 2,5-dihydroxybenzamides (8, 9) were synthesized from their corresponding methyl esters. The structures and the spectral properties of investigated salicylic acid (1), 2,4- and 2,5-dihydroxy benzoic acids (2, 3), their methyl esters (4-6) and amides (7-9) were analyzed by means of FT-IR and one- and two-dimensional homo- and heteronuclear 1H and 13C NMR spectroscopies. Comparison of FT-IR and NMR spectral data of investigated compounds showed that the spectral characteristics of 2,4-dihydroxy benzoic acid derivatives are more similar to those of 2-hydroxy benzoic acid (salicylic acid) derivatives than to those of 2,5-dihydroxy benzoic acid derivatives. The results suggest that the spatial orientation of amide protons in 2,4-dihydroxy benzamide resembles more that in salicylamide than that in 2,5-dihydroxy benzamide.

Liposomal gel with chloramphenicol: characterisation and in vitro release.

Abstract: The aim of our study was to develop a liposomal carrier system for the local treatment of bacterial vaginosis, capable to efficiently deliver entrapped drug during an extended period of time. Chloramphenicol was entrapped in liposomes composed of egg phosphatidylcholine/egg phosphatidylgycerol-sodium (9:1, molar ratio) and prepared by two different methods, the proliposome method and the polyol dilution method. Both liposome preparations were characterised and compared for particle size, polydispersity, entrapment efficiency and tested for in vitro stability in media that simulate human vaginal conditions (buffer pH 4.5 and vaginal fluid simulant). To achieve application viscosity of liposomes and to further improve their stability, liposomes prepared by the proliposome method were incorporated in the bioadhesive gel made of Carbopol 974P NF resin. In vitro release studies of liposomes incorporated in the gel have shown a prolonged release of entrapped chloramphenicol compared to control gel. Even after 24 hours of incubation in the vaginal fluid simulant, more than 40% of the originally entrapped drug was still retained in the gel. Storage stability studies have proven the ability of the Carbopol 974P NF gel to preserve the original size distribution of incorporated liposomes. All the performed experiments confirm the applicability of liposomes as a novel drug carrier system for the local treatment of bacterial vaginosis.

The antidepressant activity of Hypericum perforatum L. measured by two experimental methods on mice.

Abstract: The pharmacological approach to the treatment of depression includes a long-term employment of antidepressants, either in the form of monotherapy or as a combination of several antidepressants with various mechanisms of action. Hypericum perforatum L. (St. John's wort) is the only natural antidepressant. Several constituents of the extract, such as hypericin and hyperforin seem to be important for this effect. H. perforatum is considered to be an effective alternative to other therapeutic agents in the treatment of mild to moderate depression. The paper describes the investigation of the antidepressant effect of H. perforatum (doses 7, 35 and 70 mg kg-1 b.m.) on mice using the forced-swimming and tail suspension methods. As an indicator of the antidepressant effect, it was shown that the immobility time of animals in the forced-swimming and tail-suspension experiments was shorter, i.e. the activity of the animals was higher. With single doses of extract suspension increasing from 7, over 35 to 70 mg kg-1 of extract suspension, the antidepressant effect increased in proportion by 10.1%, 25.8% and 38.6% in the swimming method, and by 12.7%, 16.5% and 24.5% in the tai-suspension method compared to controls. H. perforatum extract displays a dose-dependent antidepressant effect at a dose as low as 7 mg kg-1. Both models have proved to be equally valuable for demonstration of substances with a potential antidepressant effect.

Phytochemical analysis of ethyl acetate extract from Astragalus corniculatus Bieb. and brain antihypoxic activity

Abstract: 1Dry ethyl acetate extract containing flavonoids was obtained from above-ground parts of Astragalus corniculatus Bieb. Seven flavonoids were isolated and identified as rutin, hyperoside, isoquercitrin, narcissin, quercetin, kaempferol and isorhamnetin for the first time. The extract was found to be practically non-toxic (acute oral toxicity > 5 g kg - 1 in mice). The extract was investigated for antihypoxic activity in two models of experimental hypoxia - haemic and circulatory. Antihypoxic activity was especially pronounced in the model of circulatory hypoxia. This effect may be attributed, at least in part, to the presence of flavonoids in the extract.

Influence of polymerization technique and experimental variables on the particle properties and release kinetics of methotrexate from poly(butylcyanoacrylate) nanoparticles.

Abstract: Poly(butylcyanoacrylate) nanoparticles were prepared by dispersion polymerization (DP) and emulsion polymerization (EP) of n-butyl cyanoacrylate monomer. The particles were characterized by infrared spectroscopy, differential scanning calorimetry, X-ray diffractometry and transmission electron microscopy. Particle properties such as size and zeta potential were determined for nanoparticles prepared by DP and EP techniques and compared. EP technique resulted in a low particle size compared to the DP. A high zeta potential was observed for nanoparticles prepared by the DP method. Incorporation of methotrexate resulted in a decrease in zeta potential in both types of nanoparticles, the decrease being greater in DP nanoparticles. Effect of experimental variables such as monomer concentration, polymerization time and temperature on drug entrapment and particle size was studied. Both types of nanoparticles showed an increase in drug entrapment with increased monomer concentrations. Variable polymerization time did not influence the drug entrapment of EP nanoparticles. Polymerization at 60 +/- 2 degrees C resulted in a decrease of drug entrapment and a great increase in the particle size of both types of nanoparticles. In vitro drug release studies showed a comparatively high release of methotrexate from DP nanoparticles suggesting the channelizing effect of dextran chains incorporated into nanoparticles during polymerization. Though the release profiles of nanoparticles appeared similar, a significant difference in release rates was found for DP and EP nanoparticles in 0.1 mol L(-1) HCl and pH 7.4 phosphate buffer (p < 0.01). Drug release data indicate that the release of methotrexate from DP and EP nanoparticles followed Fickian diffusion in 0.1 mol L(-1) HCl, while the mechanism was found anomalous in pH 7.4 phosphate buffer. An effort was also made to critically correlate the properties of nanoparticles synthesized by the above two techniques, and emphasize the importance of these characteristics in targeted drug delivery.

Synthesis and biological activity of substituted 2,4,6-s-triazines.

Abstract: Reaction of 7-hydroxy-4-methyl coumarin with amido/ imido alcohols in ethanol containing concentrated hydrochloric acid afforded 8-aralkyl amido/imido-alkyl-7-hydroxy-4-methyl-coumarins (1a-f). Interaction of 1a-f with hydrazine hydrate in pyridine resulted in 1-amino-8-aralkyl amido/imido-alkyl-7-hydroxy-4-methyl-2-oxo-quinolines (2a-f). Treatment of 2 with formaldehyde in ethanol resulted in 1,3,5-tris-(8-aralkyl amido/imido-alkyl-7-hydroxy-4-methyl-2-oxo-quinolinyl)-2,4,6-hexahydro-s-triazines (3a-c). Antiviral activity of compounds 2a-d and 3a, 3b upon Japanese encephalitis virus (JEV) and Herpes simplex virus-1 (HSV-1) was evaluated on vero cells in vitro. 3a-c were also screened for their antihypertensive activity.

Design and in vitro evaluation of new drug-in-adhesive formulations of fentanyl transdermal patches

Abstract: The present research was designed to evaluate different matrix, drug-in-adhesive and reservoir formulations of fentanyl transdermal patches. The target was to design drug-in-adhesive patches (DIAPs); a full factorial design was used. Different types and amounts of liquid, pressure-sensitive adhesives (PSAs) were used and evaluated with respect to drug release and adhesive properties. A very simple but precise method, the simplified peel 180 degrees test, was developed to measure and compare adhesive properties of transdermal patches. The results showed that release kinetics obeyed the square root of time or Higuchi model, indicating the diffusion controlled release mechanism. It was found that the amount of fentanyl needed for each 10 cm(2) three-days DIAP should be 3.3 mg. The respective amounts for reservoir and matrix patches were 2.5 and 5 mg. It was concluded that acrylic PSAs showed the best adhesion and release properties.

Preparation and evaluation of floating risedronate sodium Gelucire® 39/01 matrices

Abstract: Osteoporosis and Paget’s disease of bone are major problems in women and geriat-ric patients where antiresorptive agents are normally recommended. Despite their bene-fits, bisphosphonates suffer from very poor oral bioavailability (1–2%) (1–3). The lowbioavailability is likely due to the extensive ionization and highly hydrophilic nature ofbisphosphonates, which prevent the transcellular transport across intestinal epitheliumand favor the paracellular route (4–5). Higher localized concentration of bisphosphonateshas resulted in severe gastro-intestinal side effects such as dysphagia, esophagitis andgastric ulceration (6).To improve the bioavailability of bisphosphonates, structural modification of thebisphosphonate molecule, use of absorption enhancers and design of drug delivery sys-tems have been attempted (7–11). Surfactants such as sodium lauryl sulphate and me-dium chain fatty acid esters were found to increase bisphosphonate absorption (13, 14).Comparative evaluation of different enhancers was carried out by Raiman

Supplementation with antioxidants in the treatment of Graves' disease: the effect on the extracellular antioxidative parameters.

Abstract: In this study, the effect of supplementation with a fixed combination of antioxidants (vitamins C and E, beta-carotene and selenium) on concentrations of antioxidative parameters in serum was monitored. Measurements were performed prior to the commencement of therapy and after 30 and 60 days in patients with Graves' disease treated with methimazole. Patients who received extra supplementation with antioxidants (group A, n = 29) attained euthyroidism faster than the patients treated only with methimazole (group B, n = 28). Statistically significant differences were achieved after supplementation with antioxidants for all investigated parameters (uric acid, transferrin, ferritin), except TAS and glucose. Nevertheless, due to the fact that all measured parameters remained within the range of referent values, they may not be proposed as reliable indicators of the level of oxidative stress in Graves' disease.

Steroids and polyketides from Uvaria hamiltonii stem bark

Abstract: Two known steroids, stigmasterol and 6b-hydroxystigmasta-4,22-dien-3-one (1) and two unusual polyketides, cis-4-hydroxymellein (2) and trans-4-hydroxymellein (3) were isolated from the stem bark of Uvaria hamiltonii. The structures of the compounds were elucidated independently by high-resolution 2D-NMR techniques and confirmed by comparison with previously reported values.

2D NMR spectroscopic analyses of archangelicin from the seeds of Angelica archangelica.

Abstract: A total of six coumarins, bergapten (1), xanthotoxin (2), imperatorin (3), isoimperatorin (4), phellopterin (5) and archangelicin (6), have been isolated from an n-hexane extract of the seeds of Angelica archangelica The results of comprehensive 2D NMR analyses of archangelicin are discussed

Stability of the complexes of some lanthanides with coumarin derivatives. I. Cerium(III)-4-methyl-7-hydroxycoumarin.

Abstract: A complex of cerium(III) with 4-methyl-7-hydroxycoumarin was synthesized by mixing water solutions of cerium(III) nitrate and 4-methyl-7-hydroxycoumarin sodium salt in a metal-to-ligand molar ratio of 1:2. The complex was characterized and identified by elemental analysis, conductometry, IR, 1H and 13C NMR-spectroscopy, mass spectral data, DTA and TGA. Thermal analysis of the complex indicated the formation of a compound of the composition CeR2(OH).5H2O, R standing for the ligand. The reaction of cerium(III) with 4-methyl-7-hydroxycoumarin was studied in detail by the spectrophotometric method. The stepwise formation of two complexes, vis., CeR2+ and CeR2+, was established in the pH region studied. The equilibrium constants for 1:1 and 1:2 complexes were determined to be 10.72 and 9.22, respectively.

Optimization of chitosan film as a substitute for animal and human epidermal sheets for in vitro permeation of polar and non polar drugs.

Abstract: The present investigation is aimed at preparing chitosan films capable of simulating the flux of modal drugs, 5-fluorouracil (5-FU) and indomethacin (INDO), across rat, rabbit and human cadaver epidermal sheets. Application of statistical design revealed that the concentration of chitosan, crosslinking time and concentration of crosslinking agent significantly influenced the in vitro flux of 5-FU and INDO across chitosan films. Multiple linear regression revealed a linear influence of all these active variables on 5-FU and INDO flux. It was deduced from atomic absorption spectroscopic analyses, DSC and IR spectroscopic data that 5% (m/V) sodium tripolyphosphate (NaTPP) produced optimum crosslinking of chitosan films. The in vitro permeation of both 5-FU and INDO across optimized film formulations was found to be comparable to that obtained across rat, rabbit and human epidermal sheets. These results indicate that optimized chitosan films have a potential to be developed as a substitute for animal and human cadaver epidermal sheets for preliminary in vitro permeation studies.

Stability of the complexes of some lanthanides with coumarin derivatives. II. Neodymium(III)-acenocoumarol.

Abstract: A complex of neodymium(III) with 4-hydroxy-3[1-(4-nitrophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one (acenocoumarol) was synthesized by mixing water solutions of neodymium(III) nitrate and the ligand (metal to ligand molar ratio of 1:3). The complex was characterized and identified by elemental analysis, conductivity, IR, 1H NMR and mass spectral data. DTA and TGA were applied to study the composition of the compound. Elemental and mass spectral analysis of the complex indicated the formation of a compound of the composition NdR3 x 6H2O, where R = C19H14NO6-) The reaction of neodymium(III) with acenocoumarol was studied in detail by the spectrophotometric method. The stepwise formation of three complexes, vis., NdR2+, NdR2+ and NdR3 was established in the pH region studied (pH 3.0-7.5). The equilibrium constants for 1:1, 1:2 and 1:3 complexes were determined to be log K1 = 6.20 +/- 0.06; log K2 = 3.46 +/- 0.07 and log K2) = 2.58 +/- 0.05, respectively.

Preparation and ex vivo evaluation of TEC as an absorption enhancer for poorly absorbable compounds in colon specific drug delivery.

Abstract: In previous studies, it was established that chitosan and its quaternized derivatives are potent enhancers of hydrophilic compounds absorption across intestinal epithelia. The aim of this study was to evaluate the application of a new quaternized chitosan, triethyl chitosan (TEC), in pharmaceutical approaches. TEC was synthesized by a one step process via a 2 2 factorial design to optimize the preparation conditions. In ex vivo experiments, everted y rat colon sac was used to determine the effect of TEC on the penetration of hydrophilic compounds of different molecular masses (e.g., sodium fluorescein and brilliant blue) through colonic epithelia in comparison with chitosan at pH 7.4. These studies indicated a significant increase in absorption of sodium fluorescein and brilliant blue in the presence of TEC compared to chitosan. TEC n bearing positive charge is able to interact with the tight junctions of colon epithelia and hence increas the permeation of sodium fluorescein and brilliant blue through the tight junctions. This investigation has shown that triethyl chitosan could be used as a penetration enhancer for poorly absorbable compounds in the colon drug delivery system.

Lipophilicity study of salicylamide.

Abstract: Since lipophilicity has been recognized for its importance in QSPR (Quantitative Structure-Property Relationship) studies, efforts have been made to determine the log P (logarithm of partition coefficient in n-octanol/water) values of a number of compounds. Log P is closely related to the transport properties of drugs and their interaction with receptors. This parameter can be either determined experimentally or calculated. Because experimental measurements are time consuming and difficult, computational methods are very valuble tools for calculation of log P's for large sets of compounds in QSAR studies, particulary at the screening stage. A number of different computer programs for prediction of lipophilicity have been recently developed. In our work, nine computer programs based on different theoretical approaches for predicting log P have been compared with experimental data. Many methods for calculating log P values are reported in the literature. The most common ones are classified as »atom-type«, »fragmental« and »E-state indices« methods (1–3). Salicylamide was used as a model drug for investigations of molecular lipophilicity. It is a salicylic acid derivate mostly used in combinations with other analgesics or antipyretics. It is readily absorbed from the gastrointestinal tract and distributed to most body tissues. Although salicylamide is not as effective as acetilsalicylic acid or paracetamol, it is still used in Asia, North and South America in combined medicines for symptoms associated with cold and influenza (4).

Lignan accumulation in cell cultures of Linum strictum ssp. strictum L.

Abstract: Shoot, callus and hairy root cultures of Linum strictum ssp. strictum L. were initiated. The lignan 6-methoxypodophyllotoxin was detected and quantified.

Syntheses and characterisation of N,N'-biscarbazolyl azine and N,N'-carbazolyl hydrazine derivatives and their antimicrobial studies.

Abstract: Reaction of 1-oxo-1,2,3,4-tetrahydrocarbazoles 1a-e with hydrazine hydrate in absolute ethanol afforded N,N'-bis-carbazolylazine derivatives 2a-e. Treatment of compounds 1a-e with hydroxylamine hydrochloride in ethanol with a catalytic amount of pyridine resulted in the formation of 1-hydroxyimino-1,2,3,4-tetrahydrocarbazoles 3a-e. Reduction of 3 with hydrazine hydrate in the presence of palladized carbon afforded N,N'-carbazolyl hydrazine derivatives 4a-e. The newly formed compounds were characterized by IR, 1H NMR, mass spectra and by elemental analysis. All compounds proved to have great potentialities as antibacterial and antifungal agents due to the presence of the azine or the hydrazine group. Particularly, the chloro substituted derivatives 2e and 4e showed excellent antibacterial and antifungal activity.

FT-IR and NMR spectroscopic studies of salicylic acid derivatives. I. Gentisamide -- a metabolite of salicylamide.

Abstract: Gentisamide (GAM, 2,5-dihydroxybenzamide), a minor first-pass metabolite of salicylamide (SAM, 2-hydroxybenzamide), was studied using FT-IR, 1D and 2D homo- and heteronuclear 1H and 13C NMR spectroscopy. GAM was isolated from human urine eight hours after oral administration of SAM. FT-IR, 1H and 13C NMR spectra unequivocally confirmed the chemical structure of GAM through chemical and substituent shifts, coupling constants and connectivities in COSY, NOESY, HETCOR and HBMC spectra. From NOESY spectra of GAM in DMSO-d6, it was concluded that the amide protons are oriented toward the ortho-proton at C-6. Obtained results indicate that the presence of the additional phenol group at C-5 in GAM favours the formation of intramolecular hydrogen bonding of the O...HO type between C2-OH proton and oxygen atom of the amide group.