Sci. Pharm., Volume 77, Issue 4 (December 2009) – 12 articles , Pages 725-910

A taxonomic study into the anatomical, morphological and phytochemical differentiation of the genus Mentha L (Lamiaceae) in Bosnia & Hercegovina and Slovakia is presented. Following a population-based approach and using hierarchical cluster analyses the following basic species and hybrids corresponding to exclusive branches, i.e. groups, in the constructed hierarchies were recognized: Mentha aquatica, M. spicata, M. arvensis, M. longifolia, M. rotundifolia, M. × piperita, M. × villosa, M. × verticillata, M. × gentillis, M. × gracilis and M. pulegium. These groups were independently found by separate analyses of the sampled anatomical and morphological variation. In contrast, these anatomically and morphologically defined species exhibited a high level of phytochemical polymorphism which was largely inconsistent with the hierarchical classification. Among the analysed characters, the inflorescence type, dentation of the leaf margin, hair density, the type of capitate glandular hairs, and the main containing compound in essential oil proved most useful for the discrimination of taxa. However, most of the observed traits were not exclusive to a particular species and only the combined consideration of traits revealed coherent taxonomic groups. Basic species and hybrids are described in detail based on the anatomical, morphological and phytochemical characters used for their definition. The performed cluster analysis finally supported hypotheses on the parentage of some of the studied hybrids. Full article

In order to be applied into the body, intravenous fluids should be formulated to have an osmotic pressure similar to that of biological fluids. Physiologic acceptability of large-volume parenteral formulations in clinical practice is largely determined due to the osmotic effect of the dissolved solutes. Therefore, it is generally recommended that the labelling should list osmolarity. However, the declared osmolarity is not consistent with the principle of osmometry which measures osmolality. Then, the conversion of the measured osmolality to declared osmolarity is necessary. The conversion factor, defined as the ratio of molarity and molality of the solution, necessitates the measurement of the solution density and the expression of water content in solution. In this work, the relationship between molarity and molality of the aqueous solutions of nine parenteral solutes is studied. The equations for the interconversion between molarity and molality, employing the experimentally obtained mean molal volume of the dissolved solute, are proposed. The original equation allowing the estimation of the molal volume of the solute in aqueous solution from its true powder density is introduced and recommended for nonelectrolytes as well as the hydrates of electrolytes. Full article

The chemiluminescence of stimulated cells with phorbol myristate acetate and the production of nitric oxide after stimulation with lipopolisaccharide in the presence of the parent compounds FAA (flavone-8-acetic acid = (4-oxo-2- phenyl-4H-chromen-8-yl)acetic acid), XAA (xanthone-4-acetic acid = (9-oxo-9Hxanthen- 4-yl)acetic acid), and appropriate xanthone derivatives (1–7) was determined. Also the toxicity of the FAA, MFAA ((6-methyl-4-oxo-2-aryl-4H-chromen- 8-yl)acetic acid), XAA and 1–7 against J-774A.1 cultured cells was evaluated. Compound 5 (2-methyl-2-{[(9-oxo-9H-xanthen-2-yl)methyl]sulfanyl}- propanoic acid) was effective in inhibiting chemiluminescence of J-774A.1 cells but most of the other tested compounds stimulated the reaction. FAA and two xanthones with a methoxycarbonyl moeity slightly decreased the generation of nitric oxide at 50 μM. Most of the tested compounds (1–7) showed weak toxicity at concentration of 100 μM. Full article

[(7-Chloroquinolin-4-yl)amino]chalcone derivatives derived from the corresponding 3- or 4-[(7-chloroquinolin-4-yl)amino]acetophenone were synthesized and evaluated for in vitro antimalarial and anticancer activity. The most active compounds 12, 13, 15, 17 and 19 from the 3-substituted series displayed inhibitory values against heme cristallization in the range of 93.14 ± 1.74 – 94.93 ± 1.50 % as an antimalarial mechanism and cytotoxic effect with IC50 values of 7.93 ± 2.05, 7.11 ± 2.06 and 6.95 ± 1.62 μg/mL for 13, 17 and 19 respectively against humane prostate LNCaP tumor cells. Full article

As a continuous searching for anti-diabetic(type II) substances, seven mucilage polysaccharides from selected plants were studied as follow: aerial parts of Basella alba Linn., fruits of Hibiscus esculentus Linn., leaves of Litsea glutinosa (Lour.) C.B. Robinson, seeds of Ocimum canum Sims., seeds of Plantago ovata Forssk., fruits of Scaphium scaphigerum G. Don. and seeds of Trigonella foenum-graecum Linn. The bioactive properties for entrapping glucose, inhibiting enzyme alpha-glucosidase and free radical scavenger were in vitro studied compared to glucomannan. The physical characteristics for water holding capacity and viscosity were determined. The chemical characteristics were assayed for monosaccharide composition using methanolysis, TMSderivatization and gas chromatography. O. canum mucilage superiorly entrapped glucose compared to glucomannan. This activity was relevant to its highly viscous gelation. S. scaphigerum showed another property of alphaglucosidase inhibition. S. scaphigerum mucilage (0.5%) inhibited the enzyme activity by 82.6%, compared to 1-Deoxynorjirimycin (by 47.6%). Most mucilages, except O. canum and P. ovata, showed DPPH scavenging activity higher than glucomannan. Galacturonic acid was found in 3 from 7 mucilages namely B. alba, P. ovata and S. scaphigerum. Whereas rhamnose was common sugar found in all seven mucilages. Monosaccharide components of these mucilages were compared to the results from the previous reports. Full article

The aim of the present study was to prepare mucoadhesive nasal gels from mucilage isolated from seeds of Linum usitatissimum L. containing midazolam hydrochloride. Characterization of the isolated mucoadhesive agent was carried out, including determination of pH, swelling property, viscosity and mucoadhesive strength. The results were compared with synthetic polymers (HPMC and carbopol 934). Nasal gels of midazolam were prepared with and without enhancers and the permeation study was carried out using excised goat nasal mucosa. Permeation profiles were evaluated and histological study of nasal mucosae before and after permeation study was also conducted to determine histological change, if any. Full article

The purpose of this study was to evaluate the influence of piperine on permeation of repaglinide (RGE) across rat epidermis. In addition, the role of chitosan (CTN) and its combination with piperine was investigated for exploring the possibility of further enhancing the permeation of RGE. The permeation of RGE across excised rat epidermis was, respectively, ~4-fold, ~5-fold and ~6- fold higher when piperine (0.008% w/v), CTN (1% w/v), or piperine – CTN mixture was used as donor vehicle as compared to propylene glycol: ethanol (PG: EtOH) (7:3) mixture. The merger of T2 and T3 (lipid-specific) and obliteration of T4 (protein-specific) endothermic transitions in the thermograms of excised rat epidermis suggested overwhelming influence of these treatments on skin lipids and proteins. Further, the observed increase in intercellular space, disordering of lipid structure and corneocyte detachment indicated considerable effect on the ultrastructure of rat epidermis. The enhancement in permeation of RGE across rat epidermis excised after various treatments for different periods was correlated with the transepidermal water loss of similarly treated viable rat skin. The treatment of HaCaT cell line with piperine influenced the TJ plaque protein zonula occludens (ZO-1) as evidenced by reduced immunofluorescence of anti-TJP1 (ZO-1) antibody in confocal laser scanning microscopic studies. Treatment of HaCaT cells with CTN decreased the intensity of fluorescence on the cell walls only marginally. However, remarkable decrease in the immunofluorescence of anti-TJP1 (ZO-1) antibody was observed after treatment of HaCaT cells with mixture of piperine and CTN. The systemic delivery of RGE in rats was enhanced by 8-fold and 9.5-fold from transdermal formulations containing, respectively, piperine (0.008 % w/v) or piperine (0.008 % w/v)–CTN (1% w/v) mixture as enhancer. Overall, the observations suggested overwhelming influence of piperine and CTN on ZO-1 protein to be responsible for enhancing the percutaneous permeation of RGE. Full article

An efficient procedure for in vitro shoot production of the medicinal plant sundew (Drosera rotundifolia L.) was developed. Of three cytokinins tested, zeatin (ZEA) at a concentration of 2 μM resulted in the formation of large numbers of adventitious shoots on leaf explants. A larger size of the small shoots was achieved by combining a 2-weeks preculture with ZEA (step 1: shoot induction) with a 5-weeks main culture without plant growth regulators (step 2: shoot elongation). Liquid media were superior to semisolid media: An average of 27.4 shoots per leaf explant, and 53.3 shoots per shoot explant were achieved. The 2-step culture system with liquid media permits a comparatively cheap micropropagation of sundew as well as in vitro biomass production, with potential for scale-up. Full article

In an effort to synthesize a key intermediate, for synthesis of a variety of telithromycin derivatives a new by-product has been formed at the third stage of the synthetic scheme. The starting material, Clarithromycin, on treatment with hydrochloric acid and on benzoylation resulted in the formation of (3R,4S,5S,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-4,12,13-trihydroxy-7-methoxy- 3,5,7,9,11,13-hexamethyl-2,10-dioxooxacyclotetradecan-6-yl 3,4,6-trideoxy- 3-(dimethylamino)-2-O-(phenylcarbonyl)-β-D-xylo-hexopyranoside (2). Oxidation of this gave (3R,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl-12,13-dihydroxy- 7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxooxacyclotetradecan-6-yl 3,4,6-trideoxy-3-(dimethylamino)-2-O-(phenylcarbonyl)-β-D-xylo-hexopyranoside (3), and also an unexpected by-product 4 in equivalent amounts. The O21–H hydroxyl group in 3 was mesylated with dimethyl sulphoxide (DMSO) in pyridine leading to the precursor (3R,5R,6R,7R,9R,11R,12R,13S,14R)-14-ethyl- 12,13-dihydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-12-(methylsulfinyl)- 2,4,10-trioxooxacyclotetradecan-6-yl 3,4,6-trideoxy-3-(dimethylamino)-2-O- (phenylcarbonyl)-β-D-xylo-hexopyranoside (5), which on further treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in acetone and methylene chloride resulted in the formation of intermediate 6. The by-product 4 and the intermediate 6 were isolated and characterized as (1S,2R,5R,7R,8R,9R)-2- ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,6-dioxo-3,15-dioxabicyclo[10.2.1]- pentadeca-11,13-dien-8-yl 3,4,6-trideoxy-3-(dimethylamino)-2-O-(phenylcarbonyl)- β-D-xylo-hexopyranoside (4) and (3R,5R,6R,7R,9R,11E,13S,14R)-14- ethyl-13-hydroxy-7-methoxy-3,5,7,9,11,13-hexamethyl-2,4,10-trioxooxacyclotetradec- 11-en-6-yl 3,4,6-trideoxy-3-(dimethylamino)-2-O-(phenylcarbonyl)-β-Dxylo- hexopyranoside (6) respectively by 2D NMR and single crystal X-ray diffraction. Full article

In previous researches mebudipine and dibudipine two newly synthesized calcium channel blockers (CCBs) showed considerable relaxant effects on vascular and atrial smooth muscle cells. In this study we investigated the effects of these new drugs on vascular flow of isolated rat kidney and compare their potencies to nifedipine. It is concluded that mebudipine and dibudipine (5 μM, 10 μM) caused concentration-dependent inhibition of increases in perfusion pressure induced by phenylephrine. Mebudipine (10 μM) inhibited more greatly increases in perfusion pressure induced by phenylephrine compared to (10 μM) nifedipine. Full article

The present study investigated the protective effect of green tea and vitamin E combination on serum and heart tissue lipid profile, lipid metabolizing enzymes and histopathological changes in isoproteranol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200mg/kg, s.c.) for 2 consecutive days at an interval of 24 hrs. showed a significant increase in the levels of triglycerides (TG), total cholesterol (TC) and free fatty acids (FFA), in both serum and cardiac tissue. A rise in the levels of phospholipids (PL), low density lipoprotein (LDL) and very low density lipoprotein-cholesterol (VLDL-c) was also observed in the serum of isoproterenol-intoxicated rats. Further, a decrease in the level of high density lipoprotein-cholesterol (HDL-c) in serum and phospholipid levels, in the heart of isoproterenol-intoxicated rats was observed. Further a significant decrease in the activities of cholesterol ester synthetase (CES) and lecithin: cholesterol acyl transferase (LCAT) was shown whereas lipoprotein lipase (LPL) was found to be increased. Administration of alcoholic extract (60% polyphenols) of green tea (100 mg/kg/day, p.o.) and Vitamin E (DL-α-Tocopherol acetate) (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on day 29^th and 30^th , significantly attenuated these alterations and restored the levels of serum and heart lipids along with lipid metabolizing enzymes. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the protective effect of green tea and vitamin E in combination during ISO-induced myocardial infarction in rats. Full article

Five series of tetrahydrobenzothieno[2,3-d]pyrimidine and tetrahydrobenzothienotriazolopyrimidine derivatives have been synthesized namely: 4-(substituted amino)-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidines 4a–d, 4-substituted (methylidenehydrazino)-5,6,7,8-tetrahydro[1]benzothieno- [2,3-d]pyrimidines 6a–c, 4-(3,5-disubstituted pyrazol-1-yl)-5,6,7,8-tetrahydro- [1]benzothieno[2,3-d]pyrimidines 7a,b, 3-substituted-8,9,10,11-tetrahydro- [1]benzothieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines 8a,b, N-(phenyl or 4-substituted phenyl)-2-(8,9,10,11-tetrahydro[1]benzothieno[3,2-e][1,2,4]- triazolo[4,3-c]pyrimidin-3-ylsulfanyl)acetamides 10a–c. Preliminary antimicrobial testing revealed that compounds 4a and 10b were the most active among the tested compounds against C. albicans showing IZ = 22 mm and MIC = MBC = 31.25 μg/ml, with no significant antibacterial activity. Compounds 6b and 6c showed the highest antibacterial activity against S. aureus (IZ = 21 mm, MIC = 62.5 μg/ml, MBC = 125 μg/ml for 6b; IZ = 21 mm, MIC = MBC = 125 μg/ml for 6c). Compounds 4c and 6c showed the highest antibacterial potency against P. aeruginosa among the tested compounds (IZ = 19–20 mm, MIC = MBC = 62.5 μg/ml). None of the tested compounds showed significant antibacterial activity against E. coli. Full article