J. Serb. Chem. Soc. 74 (1) 1–13 (2009)
UDC 578.7:616.988.7:598.2; JSCS–3803; doi: 10.2298/JSC0901001M; Original scientific paper

Some novel insights into the binding of oseltAMivir and zanAMivir to H5N1 and N9 influenza virus neurAMinidases:

a homology modeling and flexible docking study
MARIJA L. MIHAJLOVIC*^,** and PETAR M. MITRASINOVIC**
*Faculty of Physical Chemistry, University of Belgrade, Studentski trg 12–16, 11000 Belgrade, Serbia

**Institute for Multidisciplinary Research, Kneza Viseslava 1, 11030 Belgrade, Serbia

(Received 2 April, revised 21 October 2008)

In the context of the recent pandemic threat by the worldwide spread of H5N1 avian influenza, novel insights into the mechanism of ligand binding and interaction between various inhibitors (zanAMivir – ZMV, oseltAMivir – OTV, 2,3-didehydro-2-deoxy-N-acetylneurAMinic acid – DANA, perAMivir – PMV) and neurAMinidases (NA) are of vital importance for the structure-based design of new anti-viral drugs. To address this issue, three-dimensional models of H5N1-NA and N9-NA were generated by homology modeling. Traditional residues within the active site throughout the fAMily of NA protein structures were found to be highly conserved in H5N1-NA. A subtle variation between lipophilic and hydrophilic environments in H5N1-NA with respect to N9-NA was observed, thus shedding more light on the high resistance of some H5N1 strains to various NA inhibitors. Based on these models, an ArgusLab4/AScore flexible docking study was performed. The conformational differences between OTV bound to H5N1-NA and OTV bound to N9-NA were structurally identified and quantified. A slight difference of less than 1 kcal mol-1 between the OTV-N9 and OTV-N1 binding free energies is in agreement with the experimentally predicted free energy difference. The conformational differences between ZMV and OTV bound to either H5N1-NA or N9-NA were structurally identified. The binding free energies of the ZMV complexes, being slightly higher than those of OTV, are not in agreement with what was previously proposed using homology modeling. The differences between ZMV and OTV are suggested to be ascribed to the presence/absence of Asn166 in the active cavity of ZMV/OTV in H5N1-NA, and to the presence/absence of Ser165 in the binding site of ZMV/OTV in N9-NA. The charge distribution was evaluated using the semi-empirical AM1 method. The trends of the AM1 charges of the ZMV and OTV side chains in the complexes deviate from those previously reported.

Keywords: H5N1 avian influenza virus neurAMinidase; homology modeling; zanAMivir; oseltAMivir; Argus Lab 4.0 docking.

J. Serb. Chem. Soc. 74 (1) 15–25 (2009)
UDC 547.533:541.124:577.15+547.96:611.018.5; JSCS–3804; doi: 10.2298/JSC0901015S; Original scientific paper

The effect of toluene on oxidative processes in rat blood
SILVANA S. STAJKOVIC, SUNCICA Z. BOROZAN* and GORDANA GADJANSKI-OMEROVIC**
Department of Food Hygiene and Technology, Faculty of Veterinary Medicine, University of Belgrade, Bulevar Oslobodjenja 18, 11000 Belgrade, Serbia

*Department of Chemistry, Faculty of Veterinary Medicine, University of Belgrade, Bulevar Oslobodjenja 18, 11000 Belgrade, Serbia

**Department of Biochemistry, Faculty of Veterinary Medicine, University of Belgrade, Bulevar Oslobodjenja 18, 11000 Belgrade, Serbia

(Received 19 February, revised 10 June 2008)

This study was designed to investigate the effects of toluene treatment on oxidative stress in rat blood. Since toluene metabolism produces reactive oxygen and nitrogen species, it was hypothesized that the toluene treatment would: 1) provoke changes in the activities of antioxidant enzymes, 2) impair the integrity of the cell membrane and 3) induce structural changes in the plasma proteins. Female Wistar rats were treated with toluene intraperitonally, at a daily dose of 0.38 mmol/kg body weight for 12 days, and 5 mmol/kg body weight for 6 days, respectively, with propylene glycol as the carrier. Toluene significantly increased superoxide dismutase activity at low doses, catalase activity at high doses and the level of erythrocytes malondialdehyde in both treated groups when compared to the control group. The nitrite (NO₂^-) level in both treated groups was not different from that in the control animals. Toluene caused oxidative modification of plasma proteins and, consequently, changes in the concentration of glycoproteins and lipoproteins when compared to the control group. The observed alterations indicate that toluene treatment might be involved in free radical processes.

Keywords: toluene; free radicals; antioxidant enzymes; protein modification.

J. Serb. Chem. Soc. 74 (1) 27–34 (2009)
UDC 582.475:547.77+547.94:615.28(497.11)(497.16); JSCS–3805; doi: 10.2298/JSC0901027M;  Original scientific paper

Pyrrolizidine alkaloids from seven wild-growing Senecio species in Serbia and Montenegro
BORIS M. MANDIC, DEJAN N. GODJEVAC*, VLADIMIR P. BESKOSKI*, MILENA R. SIMIC**, SNEZANA S. TRIFUNOVIC*, VELE V. TESEVIC, VLATKA V. VAJS* and SLOBODAN M. MILOSAVLJEVIC

Faculty of Chemistry, Studentski trg 16, P.O. Box 158, 11000 Belgrade, Serbia

*Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Njegoseva 12, 11000 Belgrade, Serbia

**Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia

(Received 17 June 2008)

The genus Senecio (fAMily Asteraceae) is one of the largest in the world. It comprises about 1100 species which are the rich source of pyrrolizidine alkaloids. Plants containing pyrrolizidine alkaloids are AMong the most important sources of human and animal exposure to plant toxins and carcinogens. The pyrrolizidine alkaloids of seven Senecio species (S. erucifolius, S. othonnae, S. wagneri, S. subalpinus, S. carpathicus, S. paludosus and S. rupestris) were studied. Fourteen alkaloids were isolated and their structures determined from spectroscopic data (¹H- and ¹³C-NMR, IR and MS). Five of them were identified in S. erucifolius, four in S. othonnae, two in S. wagneri, four in S. subalpinus, two in S. carpathicus, three in S. paludosus and three in S. rupestris. Seven pyrrolizidine alkaloids were found for the first time in particular species. The results have chemotaxonomic importance. The cytotoxic activity and antimicrobial activity of some alkaloids were also studied.

Keywords: Senecio; pyrrolizidine alkaloids; antitumor and antimicrobial activity.

J. Serb. Chem. Soc. 74 (1) 35–44 (2009)
UDC *RAMonda serbica Panč.:556.132.6:665.52/.54; JSCS–3806; doi: 10.2298/JSC0901035R; Original scientific paper

Volatiles from vegetative organs of the palaeoendemic resurrection plants RAMonda serbica Panč. And RAMonda nathaliae Panč. et Petrov.
NIKO S. RADULOVIC, POLINA D. BLAGOJEVIC, RADOSAV M. PALIC, BOJAN K. ZLATKOVIC* and BRANKA M. STEVANOVIC**
Department of Chemistry, Faculty of Science and Mathematics, University of Nis, Visegradska 33, 18000 Nis, Serbia

*Department of Biology and Ecology, Faculty of Science and Mathematics, University of Nis, Visegradska 33, 18000 Nis, Serbia

**Department of Plant Ecology and Phytogeography, Institute of Botany and Botanical Garden “Jevremovac”, Faculty of Biology, University of Belgrade, 11000 Belgrade, Takovska 43, Serbia

(Received 16 July 2008)

GC and GC/MS analyses of the essential oils hydrodistilled separately from fresh leaves and roots of RAMonda serbica and RAMonda nathaliae, together with diethyl ether extracts of their roots, enabled the identification of 82 constituents accounting for between 88.9 and 94.5 % of the oils and extracted compounds. Although phenylacetaldehyde was one of the major contributors (20.5–57.1 %) of all the oils, it was only a minor contributor to the extracts. The latter were characterized by a large AMount of squalene (R. serbica – 36.0 %; R. nathaliae – 59.4%) and steroids (R. serbica – 27.4 %; R. nathaliae – – 14.1 %). Squalene was also the most abundant compound in R. nathaliae root oil (29.0 %), but was not detected in the corresponding R. serbica oil. While the root oils and extracts of both species contained comparable AMounts of volatile fatty acids, there were significant differences in their contents in the oils hydrodistilled from the leaves of R. serbica and R. nathaliae (18.7 % and 0.6 %, respectively). The presented results provide the first insight into the unique sets of volatiles produced by these distinctive, closely related, relict taxa, which disclose their specific adaptive advantages.

Keywords: RAMonda serbica; RAMonda nathaliae; essential oil; ether extract; squalene; phenylacetaldehyde.

J. Serb. Chem. Soc. 74 (1) 45–52 (2009)

J. Serb. Chem. Soc. 74 (1) 53–60 (2009)

J. Serb. Chem. Soc. 74 (1) 61–69 (2009)

UDC 546.74–36:669.018:548.2+551.312.1; JSCS–3809; doi: 10.2298/JSC0901061K; Original scientific paper

J. Serb. Chem. Soc. 74 (1) 71–84 (2009)

UDC 537.622.4.004.12:546.47–31+546.711–31; JSCS–3810; doi: 10.2298/JSC0901071B; Original scientific paper

Ferromagnetic behaviour of the Zn–Mn–O system

BRANKA BABIC-STOJIC, DUSAN MILIVOJEVIC and JOVAN BLANUSA

Vinca Institute of Nuclear Sciences, P.O. Box 522, 11001 Belgrade, Serbia

(Received 26 May, revised 16 July 2008)

Polycrystalline Zn–Mn–O sAMples with nominal manganese concentrations x = 0.01, 0.04 and 0.10 were synthesized by a solid state reaction route using (ZnC₂O₄∙2H₂O)_1-x and (MnC₂O₄∙2H₂O)_x. Thermal treatment of the sAMples was performed in air at temperatures 673, 773, 873, 973 and 1173 K for x = 0.01 and at the temperature 773 K for x = 0.04 and 0.10. The sAMples were investigated by X-ray diffraction, thermogravimetry, differential thermal analysis, transmission electron microscopy, magnetization measurements and electron parAMagnetic resonance. X-Ray diffraction was also performed on MnO₂ thermally treated at temperatures 673, 773, 873, 973, 1073 and 1173 K. Room temperature ferromagnetism was observed in the Zn–Mn–O sAMples with x = 0.01 thermally treated at low temperatures (673 and 773 K) and in the sAMple with x = 0.04 thermally treated at 773 K. It seems that the ferromagnetic phase could originate from interactions between Mn²⁺ and acceptor defects incorporated in the ZnO crystal lattice during the thermal treatment of the sAMples.

Keywords: ZnO; diluted magnetic semiconductors; room temperature ferromagnetism.

J. Serb. Chem. Soc. 74 (1) 85–92 (2009)

UDC 628.1.033:546.19:549.73–188+541.183; JSCS–3811, doi: 10.2298/JSC0901085S; Original scientific paper

Removal of inorganic As⁵⁺ from a small drinking water system

MARJANA SIMONIC

University of Maribor, Faculty of Chemistry and Chemical Engineering, Smetanova 17, 2000 Maribor, Slovenia

(Received 20 December 2007, revised 11 April 2008)

The drinking water from a small drinking water system contained arsenic in a concentration of about 50 μg/L. Chemical analyses showed that the pentavalent form of arsenic was present. Since the MCL value is 10 μg/L, it was necessary to implement a technological treatment to make the water suitable for drinking. In order to do so, two technologies were suggested: activated alumina and a-FeOOH (TehnoArz, TA) adsorption media. Experiments using both adsorption media were performed on a laboratory scale. It was possible to remove arsenic to below 1 μg/L. The maximal adsorption capacity was found to be 12.7 mg of As⁵⁺ per grAM of a-FeOOH. Moreover, all the important physico–chemical parAMeters of the water remained practically unchanged after the treatment. Only a slight release of iron from the media was observed. The Fe–As bond was studied by means of chemical analysis and X-ray powder diffraction. Finally, in addition to showing the capability of arsenic removal by a-FeOOH, a comprehensive optimization of the technological parAMeters of the selected technology is provided.

Keywords: drinking water; arsenic; activated alumina (AA); goethite; adsorption.

J. Serb. Chem. Soc. 74 (1) 93–102 (2009)

UDC 546.17–032.6+631.415:66.095.81:66.091; JSCS–3812; doi: 10.2298/JSC0901093K; Original scientific paper

Specific transformations of mineral forms of nitrogen in acid soils

MIRJANA KRESOVIC, MIODRAG JAKOVLJEVIC, SRDJAN BLAGOJEVIC and SRBOLJUB MAKSIMOVIC*

Faculty of Agriculture, Nemanjina 6, 11080 Zemun, Belgrade, Serbia

*Institute of soil science, Teodora Drajzera 7, 11000 Belgrade, Serbia

(Received 21 March, revised 30 June 2008)

Investigations were performed on soils of different acidity, ranging in the pH interval 4.65–5.80 (in water). Changes of the mineral nitrogen forms in the exAMined soils were studied by applying short-term incubation experiments performed under aerobic conditions, with a humidity of 30 % and a temperature of 20 °C, both with and without the addition of 100 and 300 ppm NH₄–N. The results of the incubation experiments showed that retarded nitrification was present in all the exAMined soils. Increased and toxic quantities of nitrites (35.7 ppm) were formed during the incubation, which remained in the soil solution for several days, and even weeks, in spite of favorable conditions of moisture, aeration and temperature for the development of the process of chemo-autotrophic nitrification. Decelerated chemoautotrophic nitrification was the source of the occurrence of nitrite in the exAMined less acid soil (soil 1), while in soils of higher acidity (soils 2 and 3) after addition of 100 and 300 ppm NH₄–N, nitrite occurred due to chemical denitrification (chemodenitrification). Nitrites formed in the process of chemodenitrification underwent spontaneous chemical oxidation resulting in nitrate formation (chemical nitrification). The content of mineral nitrogen (NH₄ + NO₃ + NO₂–N) decreased during the incubation period, proving gaseous losses from the exAMined soils. Application of lower doses of nitrogen fertilizers could decrease nitrogen losses by denitrification as well as the occurrence of nitrite in toxic quantities in the investigated pseudogley soil.

Keywords: incubation; mineral nitrogen; nitrification; denitrification; chemodenitrification.

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