Maya Georgieva - Academia.edu (original) (raw)

Papers by Maya Georgieva

Letters in Drug Design & Discovery, 2010

Twelve pyrrole hydrazones were synthesized and evaluated in vitro as inhibitors of Mycobacterium ... more Twelve pyrrole hydrazones were synthesized and evaluated in vitro as inhibitors of Mycobacterium tuberculosis H 37 Rv with IC50 and IC90 to 5.92 μg/ml and 9.37 μg/ml respectively. The most active 12d (ethyl 5-(4-chlorophenyl)-2-methyl-1-(4-(2-((5-nitrofuran-2-yl)methylene)hydrazinyl)-4-oxobutyl)-1H-pyrrole-3-carboxylate) has IC90 value of 9.372 μg/ml. The derived second order QSAR model favors moderate molecular surfaces in a combination with electronaccepting substituents in the aromatic hydrazone moiety.

Anti-Cancer Agents in Medicinal Chemistry, 2015

A new series of N-substituted 1-benzyltheobromine-8-thioacetamides were designed and synthesized.... more A new series of N-substituted 1-benzyltheobromine-8-thioacetamides were designed and synthesized. Their anti-proliferative activity against human chronic myelocytic leukemia cell K562, human T-cell leukemia cell SKW-3 and human acute myeloid leukemia HL-60 was evaluated. For the tested compounds a concentration-dependent cytotoxic activity was observed, with 7g outlined as the most active compound within the series. The targed compounds were obtained in yields of 56 to 85% and their structures were elucidated by FTIR, 1H NMR, 13C NMR and microanalyses. The compounds purity was proven by elemental analysis and spectral data. In general, the compounds showed low hepatotoxicity on sub-cellular and cellular level. On isolated rat microsomes only 7d showed toxic effect while theobromine, 1-benzyl-theobromine-thioacetic acid (BTTA) and the other new theobromine derivatives were devoid of toxicity. In isolated rat hepatocytes, when compared to theobromine and BTTA, 7f showed lower cytotoxic effects, 7d exerted higher cytotoxicity. The results indicate 7g as a promising structure for design of future compounds with low hepatotoxicity and good antiproliferative activity.ts.

Oxygen is one of the most important and indispensable elements, since life molecules on Earth can... more Oxygen is one of the most important and indispensable elements, since life molecules on Earth can, under certain situations, produce from it constantly in the human body toxic molecules, called free radicals and/or other reactive oxygen species (ROS). ROS play a dual role in biological systems, since they can be either harmful or beneficial to living systems. These highly reactive species capable of wide spread, indiscriminate oxidation and peroxidation of proteins, lipids and DNA which can lead to significant cellular damage and even tissue and/or organ failure. However, it is well known fact, that many of the ROS-mediated responses actually protect the cells against oxidative stress. On the other hand, over-production of ROS has the potential to cause damage. In addition currently some increasing evidence appeared showing that oxidative stress is associated with the pathogenesis of number diseases, like neurodegenerative disorders, cardiovascular diseases, neuropsychiatric disorde...

DESCRIPTION Abstract. A fast, simple and fully automated RP-HPLC analytical method with UV detect... more DESCRIPTION Abstract. A fast, simple and fully automated RP-HPLC analytical method with UV detection for determination of indomethacin substance and its degradation product 4-chlorobenzoic acid was modified and validated. The analysis was performed at isocratic conditions, applying a mobile phase of acetonitrile and 0.5% ortophosphoric acid (50:50, v/v) at flow rate 1.5 ml/min. The system’s suitability parameters and validation parameters were set up. The modified and validated method was successfully applied for determination of stability of indomethacin substance under a model of physiological conditions. The analyzed indomethacin substance was established to be stable in acid and neutral media, while a hydrolysis occurs in alkali media. A first order rate constant for the degradation of indomethacin in alkali media was determined.

Letters in Drug Design & Discovery, 2010

ABSTRACT Twelve pyrrole hydrazones were synthesized and evaluated in vitro as inhibitors of Mycob... more ABSTRACT Twelve pyrrole hydrazones were synthesized and evaluated in vitro as inhibitors of Mycobacterium tuberculosis H37Rv with IC50 and IC90 to 5.92 μg/ml and 9.37 μg/ml respectively. The most active 12d (ethyl 5-(4-chlorophenyl)-2-methyl-1-(4-(2-((5-nitrofuran-2-yl)methylene)hydrazinyl)-4-oxobutyl)-1H-pyrrole-3-carboxylate) has IC90 value of 9.372 μg/ml. The derived second order QSAR model favors moderate molecular surfaces in a combination with electronaccepting substituents in the aromatic hydrazone moiety.

Scripta Scientifica Pharmaceutica, 2014

Five-stage synthetic scheme for obtaining of N-substituted 1-benzyltheobromine-8-thioglicolacetam... more Five-stage synthetic scheme for obtaining of N-substituted 1-benzyltheobromine-8-thioglicolacetamides was described. The intermediate compound 1-benzyl-8-bromotheobromine was synthesized using aliquat 336 as phase transfer catalyst in very good yield. Five amide derivatives of 1-benzyltheobromine-8-thioglicolyc acid were obtained in yields of 61 to 81%. The structures of the studied compounds were established by FTIR, 1 H NMR spectral data. In order to estimate the drug-likeness of compounds 7a-e, a theoretical calculation of some molecular descriptors was made using two approaches: the Lipinski's Rule of Five limitations and the OSIRIS Property Explorer evaluation score. The comparison of the calculated results indicate that only one compound violates the Lipinski's Rule of Five parameters -7c, which makes it unsuitable for further structural optimizations. On the other hand compound 7e shows the highest drug like properties with Fragment Based Druglikeness score of 2.58 and total Drug score of 0.43 which are better than the same scores of parent compound theobromine.

Called "the building blocks of life", amino acids have long played and important role i... more Called "the building blocks of life", amino acids have long played and important role in human nutrition and health maintenance. The amino acids have a biological activity and are components in foods and food additives. The food additives contains a different variety of essential and non-essential amino ac-ids that play a critical role in metabolizing nutrients, building muscle tissue, and protecting the body against disease. The fact that one food additive has a plant or animal origin, does not make it safe. Mostly there is no regulatory analytical control, qualitative and quantitative analysis of the input amino acids in food ad-ditives, leading to compromise of quality and in some cases to adverse risk. This paper reviews the most used manufacturing methods for the production of some amino acids and variety of analytical methods for their characterization. Introduction Amino acids are biologically important organic compounds that contain amine and carboxylic acid functi...

The synthesis of methylxanthine derivatives could be a good approach to develop new analogues wit... more The synthesis of methylxanthine derivatives could be a good approach to develop new analogues with similar or novel pharmacological profiles including antiproliferative activity. The synthesis of four derivatives of 1,3,7-trimethylxanthine with substituents containing allantoin and saccharine in the side chain on 8th position in the xanthine ring was studied. The theoretical structure of the investigated compounds was compared to the crystallographic data for caffeine, allantoin and saccharin and a good agreement between theoretical and experimental data was established. The results from FTIR, 1H-NMR and 13C-NMR spectral analysis confirmed the proposed structures of the tested compounds. The theoretical UV spectra correspond to the experimentally observed. It was proven that in compounds 6a,b, the 2,5-dioxo-4-ureidoimidazolidine is bound to the alkyl side chain at position 1, and not at position 3. The estimated redox potential for all compounds is about 8.31–8.73 eV. According to t...

A series of monoterpenic ester derivatives of theophylline 7-acetic acid with a chosen monoter-pe... more A series of monoterpenic ester derivatives of theophylline 7-acetic acid with a chosen monoter-pene alcohol were synthesized, according to two synthetic pathways. The structure of the new products was elucidated with TLC characteristics, IR and 1 H-NMR spectra. By evaluation of some electro-optical param-eters of the studied compounds was established, that the hydrophilicity and the values of HOMO/LUMO energies are of great importance for the biological activity. An elucidation of their drug likeness was made, based on Lipinski's Rule of Five parameters. It was determined, that the newly synthesized products are in good agreement with Lipinski's Rule of Five limitations, which is a premise for good pharmacokinetics. This was also conformed from the results for the %ABS parameter, whereas the target compounds are with commensurable %ABS. The possible enzymatic activity of the newly obtained products was determined. It was found, that com-pound 3c expresses good enzyme inhibit...

Oxidation Communications

Novel computational strategies are continuously being demanded by the pharmaceutical industry to ... more Novel computational strategies are continuously being demanded by the pharmaceutical industry to assist, improve and speed up the drug discovery process. In this scenario chemoinformatics provide reliable mathematical tools to derive quantitative structure–activity relationships (QSARs), able to describe the correlation between molecular descriptors and various experimental profiles of the compounds. In the last years, nonlinear machine learning approaches have demonstrated a noteworthy predictive capability in several QSAR applications, confirming their superiority over the traditional linear methodologies. Particularly the feasibility of the classification approach has been highlighted in solving complex tasks. Moreover, the introduction of the autocorrelation concept in chemistry allows the structural comparison of the molecules by using a vectorial fixed-length representation to serve as effective molecular descriptor. In the present work we have investigated the potentialities ...

Modern medicine has a vast set of antibacterial means-mainly antibiotics. They are the most fre-q... more Modern medicine has a vast set of antibacterial means-mainly antibiotics. They are the most fre-quently prescribed medicines in the therapeutical practice. The β-lactam antibiotics are most often indicated for prophylaxis and treatment of bacterial infections caused by susceptible organisms. The analysis of these substances is a challenge due to their sensitivity and instability under different condi-tions. Keeping this in mind some chemical methods have often been applied as methods for quantitation. On the other hand, in an attempt to protect the structure, a number of instrumental methods have been de-veloped, based on UV/VIS spectrometry and different chromatographic techniques. Thus in this review we make an analytical survey comparisson of the described in the literarute methods for analysis of beta -lactam antibiotics, applied alone or in combinations, as antibacterial products. Introduction The beta-lactam antibiotics are an essential part in the treatment of infections. Che...

Disorders of the central nervous system currently affect over 1.5 billion people worldwide and ac... more Disorders of the central nervous system currently affect over 1.5 billion people worldwide and account for about a third of the global disease burden. The prevalence in recent years and the variety of mood disorders stimulate the development of new agents for their treatment. 1-Arylpiperazines are well known 5-HT receptor ligands with 5-HT1A and/or 5-HT2A affi nity. The inclusion of a complex heterocyclic fragment through a polymethylene spacer at piperazine position N4 often leads to more potent ligands in both 5-HT1A and 5-HT2A affi nities. The results described in literature permit an assumption that the structure of the substituent in positions 1 and 7 of purine-2,6-dione may be regarded as important factor involved in the control of 5HT1A affi nity. From the presented investigations may be concluded, that the modifi cation within the aryl fragment had typical infl uence on 5-HT1A receptor activity. Substitutents at the ortho position of the phenyl ring are well accepted, and th...

Modified and optimized methods for synthesis of 8-bromocaffeine, caffeine-8-thioglycolic acid and... more Modified and optimized methods for synthesis of 8-bromocaffeine, caffeine-8-thioglycolic acid and its ester derivatives were developed. The modification of 8-bromocaffeine synthesis included a change in the brominating agent, which resulted in cost reduction. Some investigations were performed on the influence of the catalyst type and concentration, using a modеl reaction of esterification of caffeine-8-thioglycolic acid with methanol. It was established that the application of the ion-exchane resign Wofatit P as catalyst resulted into significant increase of the ester yields and facilitation of its isolation. Thus the optimal parameters of the caffeine-8-thioglycolic acid esterification were: 35 fold excess of methanol, temperature of 65°C and catalyst Wofatit P at 4 wt. % of total acid weight. Thus four other caffeine-8-thioglycolates were synthesized with high yields (78-98%) and purity and their structures were confirmed.

The present study describes HPLC/UV method with varying conditions (mobile phases content, flow r... more The present study describes HPLC/UV method with varying conditions (mobile phases content, flow rates, solvents) for quantitation of water-soluble vitamins (WSV) in supplement mixtures. The method was optimized in respects of analytical and chromatographic parameters such as retention time, symmetry factors, column efficiency as number of theoretical plates, capacity factors, specificity, repeatability, LoD, LoQ and linearity. The performance of these method distinguished with excellent application in the assay tests of WSVs in supplement mixtures containing Thiamine, Riboflavine, Pyridoxine, Niacinamide and Folic acid.

Using the web-based tool PharmMapper, based on the reverse pharmacophore approach, we aligned 7 n... more Using the web-based tool PharmMapper, based on the reverse pharmacophore approach, we aligned 7 newly synthesized pipreazine amide derivatives to 2241 human protein targets, from which the top 300 targets were analyzed. By the flexible alignment of these structures the calculated and recorded pharmacophores were obtained and the candidate targets were prioritized, based on the corresponding fit values and z-scores. Of high interest was the model derived for activity to -secretase 1, since it was categorized as the probable target for the compounds of interest. The most significant pharmacophoric parameter was established to be the hydrophobicity of the molecule, whereas for compound 2f, with highest fit score, the significance of this parameter is greatest. It may be concluded that structures with 4-7 hydrophobic positions and aromatic ring or four carbon atoms in the side chain are of interest in further evaluation of piperazine bearing structures with -secretase 1 activity.

Unlike antibiotics which mean “to destroy life,” probiotics literally means “life giving”. Probio... more Unlike antibiotics which mean “to destroy life,” probiotics literally means “life giving”. Probiotics are friendly bacteria. When consumed, probiotics confer beneficial effects to the host. It influences the homeostasis and controls various gastrointestinal disorders. Probiotic ingestion can be a preventive approach for maintaining the balance of the intestinal microbial flora. Currently, probiotic foods, dietary supplements and beverages are accepted globally due to development in the relationship between nutrition and health, their promising health benefits and negligible side effects. Therefore, the need has arisen for more effective quality control methods aiming at detecting adulteration. Deciding which supplements you should buy is a tricky business. There are thousands of options to choose from, but very little reliable information to help you weed out the best from the rest.

International Journal of Food Sciences and Nutrition

The need for analytical control of food supplements and " energy " drinks containing am... more The need for analytical control of food supplements and " energy " drinks containing amino acids is huge. In the literature there are describes various analytical techniques for their qualitative and quantitative analysis. Most preferred methods is HPLC because of its range, accuracy and speed. Despite the wide variety of methods, there isn't coherent analytical system associated with the standardization of food additives containing amino acids.

Optics and Spectroscopy, 2013

Correlations between experimental chemical shifts and GIAO-calculated isotropic shielding constan... more Correlations between experimental chemical shifts and GIAO-calculated isotropic shielding constants of hydrogen and carbon atoms were obtained for a series of imidazole derivatives with antiproloferative activity, in order to assess the performance of NMR spectral calculations, using both HF and DFT-B3LYP level of theory with different basis sets. The influence of the choice of the method and the basis set on the chemical shift was investigated. The theoretical values were compared with the experimental data. The experimental shifts for carbons are in better agreement with the HF/6-311 G(d) and B3LYP/6-31 G(d) calculations, whereas for protons the differences are almost negligible. The calculated root mean square values for 1H shifts indicate that the 6-311+G(2d,p) basis set provides better fit for chemical shifts than the other basis sets. The obtained b values differ with statistical significance from zero (P < 0.001), which on the linear model used is adequate and correctly describes the dependence between the experimental and the calculated values of the corresponding chemical shifts. The analysis of the obtained pharmacological data for the newly synthesized imidazole derivatives shows that the target structures possess antiproliferative activity and they may be recognised as leading structures for future development of new anti-neoplastic agents.

Letters in Drug Design & Discovery, 2010

Twelve pyrrole hydrazones were synthesized and evaluated in vitro as inhibitors of Mycobacterium ... more Twelve pyrrole hydrazones were synthesized and evaluated in vitro as inhibitors of Mycobacterium tuberculosis H 37 Rv with IC50 and IC90 to 5.92 μg/ml and 9.37 μg/ml respectively. The most active 12d (ethyl 5-(4-chlorophenyl)-2-methyl-1-(4-(2-((5-nitrofuran-2-yl)methylene)hydrazinyl)-4-oxobutyl)-1H-pyrrole-3-carboxylate) has IC90 value of 9.372 μg/ml. The derived second order QSAR model favors moderate molecular surfaces in a combination with electronaccepting substituents in the aromatic hydrazone moiety.

Anti-Cancer Agents in Medicinal Chemistry, 2015

A new series of N-substituted 1-benzyltheobromine-8-thioacetamides were designed and synthesized.... more A new series of N-substituted 1-benzyltheobromine-8-thioacetamides were designed and synthesized. Their anti-proliferative activity against human chronic myelocytic leukemia cell K562, human T-cell leukemia cell SKW-3 and human acute myeloid leukemia HL-60 was evaluated. For the tested compounds a concentration-dependent cytotoxic activity was observed, with 7g outlined as the most active compound within the series. The targed compounds were obtained in yields of 56 to 85% and their structures were elucidated by FTIR, 1H NMR, 13C NMR and microanalyses. The compounds purity was proven by elemental analysis and spectral data. In general, the compounds showed low hepatotoxicity on sub-cellular and cellular level. On isolated rat microsomes only 7d showed toxic effect while theobromine, 1-benzyl-theobromine-thioacetic acid (BTTA) and the other new theobromine derivatives were devoid of toxicity. In isolated rat hepatocytes, when compared to theobromine and BTTA, 7f showed lower cytotoxic effects, 7d exerted higher cytotoxicity. The results indicate 7g as a promising structure for design of future compounds with low hepatotoxicity and good antiproliferative activity.ts.

Oxygen is one of the most important and indispensable elements, since life molecules on Earth can... more Oxygen is one of the most important and indispensable elements, since life molecules on Earth can, under certain situations, produce from it constantly in the human body toxic molecules, called free radicals and/or other reactive oxygen species (ROS). ROS play a dual role in biological systems, since they can be either harmful or beneficial to living systems. These highly reactive species capable of wide spread, indiscriminate oxidation and peroxidation of proteins, lipids and DNA which can lead to significant cellular damage and even tissue and/or organ failure. However, it is well known fact, that many of the ROS-mediated responses actually protect the cells against oxidative stress. On the other hand, over-production of ROS has the potential to cause damage. In addition currently some increasing evidence appeared showing that oxidative stress is associated with the pathogenesis of number diseases, like neurodegenerative disorders, cardiovascular diseases, neuropsychiatric disorde...

DESCRIPTION Abstract. A fast, simple and fully automated RP-HPLC analytical method with UV detect... more DESCRIPTION Abstract. A fast, simple and fully automated RP-HPLC analytical method with UV detection for determination of indomethacin substance and its degradation product 4-chlorobenzoic acid was modified and validated. The analysis was performed at isocratic conditions, applying a mobile phase of acetonitrile and 0.5% ortophosphoric acid (50:50, v/v) at flow rate 1.5 ml/min. The system’s suitability parameters and validation parameters were set up. The modified and validated method was successfully applied for determination of stability of indomethacin substance under a model of physiological conditions. The analyzed indomethacin substance was established to be stable in acid and neutral media, while a hydrolysis occurs in alkali media. A first order rate constant for the degradation of indomethacin in alkali media was determined.

Letters in Drug Design & Discovery, 2010

ABSTRACT Twelve pyrrole hydrazones were synthesized and evaluated in vitro as inhibitors of Mycob... more ABSTRACT Twelve pyrrole hydrazones were synthesized and evaluated in vitro as inhibitors of Mycobacterium tuberculosis H37Rv with IC50 and IC90 to 5.92 μg/ml and 9.37 μg/ml respectively. The most active 12d (ethyl 5-(4-chlorophenyl)-2-methyl-1-(4-(2-((5-nitrofuran-2-yl)methylene)hydrazinyl)-4-oxobutyl)-1H-pyrrole-3-carboxylate) has IC90 value of 9.372 μg/ml. The derived second order QSAR model favors moderate molecular surfaces in a combination with electronaccepting substituents in the aromatic hydrazone moiety.

Scripta Scientifica Pharmaceutica, 2014

Five-stage synthetic scheme for obtaining of N-substituted 1-benzyltheobromine-8-thioglicolacetam... more Five-stage synthetic scheme for obtaining of N-substituted 1-benzyltheobromine-8-thioglicolacetamides was described. The intermediate compound 1-benzyl-8-bromotheobromine was synthesized using aliquat 336 as phase transfer catalyst in very good yield. Five amide derivatives of 1-benzyltheobromine-8-thioglicolyc acid were obtained in yields of 61 to 81%. The structures of the studied compounds were established by FTIR, 1 H NMR spectral data. In order to estimate the drug-likeness of compounds 7a-e, a theoretical calculation of some molecular descriptors was made using two approaches: the Lipinski's Rule of Five limitations and the OSIRIS Property Explorer evaluation score. The comparison of the calculated results indicate that only one compound violates the Lipinski's Rule of Five parameters -7c, which makes it unsuitable for further structural optimizations. On the other hand compound 7e shows the highest drug like properties with Fragment Based Druglikeness score of 2.58 and total Drug score of 0.43 which are better than the same scores of parent compound theobromine.

Called "the building blocks of life", amino acids have long played and important role i... more Called "the building blocks of life", amino acids have long played and important role in human nutrition and health maintenance. The amino acids have a biological activity and are components in foods and food additives. The food additives contains a different variety of essential and non-essential amino ac-ids that play a critical role in metabolizing nutrients, building muscle tissue, and protecting the body against disease. The fact that one food additive has a plant or animal origin, does not make it safe. Mostly there is no regulatory analytical control, qualitative and quantitative analysis of the input amino acids in food ad-ditives, leading to compromise of quality and in some cases to adverse risk. This paper reviews the most used manufacturing methods for the production of some amino acids and variety of analytical methods for their characterization. Introduction Amino acids are biologically important organic compounds that contain amine and carboxylic acid functi...

The synthesis of methylxanthine derivatives could be a good approach to develop new analogues wit... more The synthesis of methylxanthine derivatives could be a good approach to develop new analogues with similar or novel pharmacological profiles including antiproliferative activity. The synthesis of four derivatives of 1,3,7-trimethylxanthine with substituents containing allantoin and saccharine in the side chain on 8th position in the xanthine ring was studied. The theoretical structure of the investigated compounds was compared to the crystallographic data for caffeine, allantoin and saccharin and a good agreement between theoretical and experimental data was established. The results from FTIR, 1H-NMR and 13C-NMR spectral analysis confirmed the proposed structures of the tested compounds. The theoretical UV spectra correspond to the experimentally observed. It was proven that in compounds 6a,b, the 2,5-dioxo-4-ureidoimidazolidine is bound to the alkyl side chain at position 1, and not at position 3. The estimated redox potential for all compounds is about 8.31–8.73 eV. According to t...

A series of monoterpenic ester derivatives of theophylline 7-acetic acid with a chosen monoter-pe... more A series of monoterpenic ester derivatives of theophylline 7-acetic acid with a chosen monoter-pene alcohol were synthesized, according to two synthetic pathways. The structure of the new products was elucidated with TLC characteristics, IR and 1 H-NMR spectra. By evaluation of some electro-optical param-eters of the studied compounds was established, that the hydrophilicity and the values of HOMO/LUMO energies are of great importance for the biological activity. An elucidation of their drug likeness was made, based on Lipinski's Rule of Five parameters. It was determined, that the newly synthesized products are in good agreement with Lipinski's Rule of Five limitations, which is a premise for good pharmacokinetics. This was also conformed from the results for the %ABS parameter, whereas the target compounds are with commensurable %ABS. The possible enzymatic activity of the newly obtained products was determined. It was found, that com-pound 3c expresses good enzyme inhibit...

Oxidation Communications

Novel computational strategies are continuously being demanded by the pharmaceutical industry to ... more Novel computational strategies are continuously being demanded by the pharmaceutical industry to assist, improve and speed up the drug discovery process. In this scenario chemoinformatics provide reliable mathematical tools to derive quantitative structure–activity relationships (QSARs), able to describe the correlation between molecular descriptors and various experimental profiles of the compounds. In the last years, nonlinear machine learning approaches have demonstrated a noteworthy predictive capability in several QSAR applications, confirming their superiority over the traditional linear methodologies. Particularly the feasibility of the classification approach has been highlighted in solving complex tasks. Moreover, the introduction of the autocorrelation concept in chemistry allows the structural comparison of the molecules by using a vectorial fixed-length representation to serve as effective molecular descriptor. In the present work we have investigated the potentialities ...

Modern medicine has a vast set of antibacterial means-mainly antibiotics. They are the most fre-q... more Modern medicine has a vast set of antibacterial means-mainly antibiotics. They are the most fre-quently prescribed medicines in the therapeutical practice. The β-lactam antibiotics are most often indicated for prophylaxis and treatment of bacterial infections caused by susceptible organisms. The analysis of these substances is a challenge due to their sensitivity and instability under different condi-tions. Keeping this in mind some chemical methods have often been applied as methods for quantitation. On the other hand, in an attempt to protect the structure, a number of instrumental methods have been de-veloped, based on UV/VIS spectrometry and different chromatographic techniques. Thus in this review we make an analytical survey comparisson of the described in the literarute methods for analysis of beta -lactam antibiotics, applied alone or in combinations, as antibacterial products. Introduction The beta-lactam antibiotics are an essential part in the treatment of infections. Che...

Disorders of the central nervous system currently affect over 1.5 billion people worldwide and ac... more Disorders of the central nervous system currently affect over 1.5 billion people worldwide and account for about a third of the global disease burden. The prevalence in recent years and the variety of mood disorders stimulate the development of new agents for their treatment. 1-Arylpiperazines are well known 5-HT receptor ligands with 5-HT1A and/or 5-HT2A affi nity. The inclusion of a complex heterocyclic fragment through a polymethylene spacer at piperazine position N4 often leads to more potent ligands in both 5-HT1A and 5-HT2A affi nities. The results described in literature permit an assumption that the structure of the substituent in positions 1 and 7 of purine-2,6-dione may be regarded as important factor involved in the control of 5HT1A affi nity. From the presented investigations may be concluded, that the modifi cation within the aryl fragment had typical infl uence on 5-HT1A receptor activity. Substitutents at the ortho position of the phenyl ring are well accepted, and th...

Modified and optimized methods for synthesis of 8-bromocaffeine, caffeine-8-thioglycolic acid and... more Modified and optimized methods for synthesis of 8-bromocaffeine, caffeine-8-thioglycolic acid and its ester derivatives were developed. The modification of 8-bromocaffeine synthesis included a change in the brominating agent, which resulted in cost reduction. Some investigations were performed on the influence of the catalyst type and concentration, using a modеl reaction of esterification of caffeine-8-thioglycolic acid with methanol. It was established that the application of the ion-exchane resign Wofatit P as catalyst resulted into significant increase of the ester yields and facilitation of its isolation. Thus the optimal parameters of the caffeine-8-thioglycolic acid esterification were: 35 fold excess of methanol, temperature of 65°C and catalyst Wofatit P at 4 wt. % of total acid weight. Thus four other caffeine-8-thioglycolates were synthesized with high yields (78-98%) and purity and their structures were confirmed.

The present study describes HPLC/UV method with varying conditions (mobile phases content, flow r... more The present study describes HPLC/UV method with varying conditions (mobile phases content, flow rates, solvents) for quantitation of water-soluble vitamins (WSV) in supplement mixtures. The method was optimized in respects of analytical and chromatographic parameters such as retention time, symmetry factors, column efficiency as number of theoretical plates, capacity factors, specificity, repeatability, LoD, LoQ and linearity. The performance of these method distinguished with excellent application in the assay tests of WSVs in supplement mixtures containing Thiamine, Riboflavine, Pyridoxine, Niacinamide and Folic acid.

Using the web-based tool PharmMapper, based on the reverse pharmacophore approach, we aligned 7 n... more Using the web-based tool PharmMapper, based on the reverse pharmacophore approach, we aligned 7 newly synthesized pipreazine amide derivatives to 2241 human protein targets, from which the top 300 targets were analyzed. By the flexible alignment of these structures the calculated and recorded pharmacophores were obtained and the candidate targets were prioritized, based on the corresponding fit values and z-scores. Of high interest was the model derived for activity to -secretase 1, since it was categorized as the probable target for the compounds of interest. The most significant pharmacophoric parameter was established to be the hydrophobicity of the molecule, whereas for compound 2f, with highest fit score, the significance of this parameter is greatest. It may be concluded that structures with 4-7 hydrophobic positions and aromatic ring or four carbon atoms in the side chain are of interest in further evaluation of piperazine bearing structures with -secretase 1 activity.

Unlike antibiotics which mean “to destroy life,” probiotics literally means “life giving”. Probio... more Unlike antibiotics which mean “to destroy life,” probiotics literally means “life giving”. Probiotics are friendly bacteria. When consumed, probiotics confer beneficial effects to the host. It influences the homeostasis and controls various gastrointestinal disorders. Probiotic ingestion can be a preventive approach for maintaining the balance of the intestinal microbial flora. Currently, probiotic foods, dietary supplements and beverages are accepted globally due to development in the relationship between nutrition and health, their promising health benefits and negligible side effects. Therefore, the need has arisen for more effective quality control methods aiming at detecting adulteration. Deciding which supplements you should buy is a tricky business. There are thousands of options to choose from, but very little reliable information to help you weed out the best from the rest.

International Journal of Food Sciences and Nutrition

The need for analytical control of food supplements and " energy " drinks containing am... more The need for analytical control of food supplements and " energy " drinks containing amino acids is huge. In the literature there are describes various analytical techniques for their qualitative and quantitative analysis. Most preferred methods is HPLC because of its range, accuracy and speed. Despite the wide variety of methods, there isn't coherent analytical system associated with the standardization of food additives containing amino acids.

Optics and Spectroscopy, 2013

Correlations between experimental chemical shifts and GIAO-calculated isotropic shielding constan... more Correlations between experimental chemical shifts and GIAO-calculated isotropic shielding constants of hydrogen and carbon atoms were obtained for a series of imidazole derivatives with antiproloferative activity, in order to assess the performance of NMR spectral calculations, using both HF and DFT-B3LYP level of theory with different basis sets. The influence of the choice of the method and the basis set on the chemical shift was investigated. The theoretical values were compared with the experimental data. The experimental shifts for carbons are in better agreement with the HF/6-311 G(d) and B3LYP/6-31 G(d) calculations, whereas for protons the differences are almost negligible. The calculated root mean square values for 1H shifts indicate that the 6-311+G(2d,p) basis set provides better fit for chemical shifts than the other basis sets. The obtained b values differ with statistical significance from zero (P < 0.001), which on the linear model used is adequate and correctly describes the dependence between the experimental and the calculated values of the corresponding chemical shifts. The analysis of the obtained pharmacological data for the newly synthesized imidazole derivatives shows that the target structures possess antiproliferative activity and they may be recognised as leading structures for future development of new anti-neoplastic agents.