TY  - JOUR
AU  - Kovačević, Strahinja
AU  - Karadzić-Banjac, Milica
AU  - Podunavac-Kuzmanović, Sanja
AU  - Milošević, Nataša
AU  - Curcić, Jelena
AU  - Vulić, Jelena
AU  - Seregelj, Vanja
AU  - Banjac, Nebojša
AU  - Ušćumlić, Gordana
PY  - 2020
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5885
AB  - The present study is focused on a series of newly synthesized 1-aryl-3-ethyl-3-methylsuccinimide derivatives, as potential anticonvulsants. The retention behavior of eleven succinimide derivatives was determined by using reversed phase high performance liquid chromatography (RP-HPLC) and reversed phase high performance thin layer chromatography (RP-HPTLC). The estimated retention behavior was correlated with partition (logP) and distribution coefficients (logD). These high correlations pointed out that the determined retention parameters (logK(0) and R-M(0)) can be considered chromatographic (anisotropic) lipophilicity of the studied succinimide derivatives. The structural properties, which dominantly affect the chromatographic lipophilicity, were determined as well. The significant correlations between the chromatographic lipophilicity and plasma protein binding (PPB), Madin-Darby Canine Kidney (MDCK) cells permeability, volume of distribution (Vd) and absorption constant (Ka) indicate the strong influence of lipophilicity on pharmacokinetics of 1-aryl-3-ethyl-3-methylsuccinimide derivatives. These derivatives have also been tested applying Comprehensive Medicinal Chemistry (CMC) drug-like rules which confirmed their drug-like properties. Besides, their blood-brain penetration (BBB) ability has been estimated applying the set of Clark's rules and by using Pre-ADMET software. Regarding toxicity, it was predicted that only one compound from the set might have toxic effects by blocking the hERG potassium channel. The present study reveals which molecular features in the structure of novel succinimide derivatives could be crucial for their lipophilicity, and consequently for their pharmacokinetic properties. The results indicate that the newly synthesized series of succinimide derivatives should be further considered in design of novel anticonvulsants.
PB  - Elsevier Sci Ltd, Oxford
T2  - Computational Biology and Chemistry
T1  - Chromatographic and computational screening of anisotropic lipophilicity and pharmacokinetics of newly synthesized 1-aryl-3-ethyl-3-methylsuccinimides
VL  - 84
DO  - 10.1016/j.compbiolchem.2019.107161
ER  - 

@article{
author = "Kovačević, Strahinja and Karadzić-Banjac, Milica and Podunavac-Kuzmanović, Sanja and Milošević, Nataša and Curcić, Jelena and Vulić, Jelena and Seregelj, Vanja and Banjac, Nebojša and Ušćumlić, Gordana",
year = "2020",
abstract = "The present study is focused on a series of newly synthesized 1-aryl-3-ethyl-3-methylsuccinimide derivatives, as potential anticonvulsants. The retention behavior of eleven succinimide derivatives was determined by using reversed phase high performance liquid chromatography (RP-HPLC) and reversed phase high performance thin layer chromatography (RP-HPTLC). The estimated retention behavior was correlated with partition (logP) and distribution coefficients (logD). These high correlations pointed out that the determined retention parameters (logK(0) and R-M(0)) can be considered chromatographic (anisotropic) lipophilicity of the studied succinimide derivatives. The structural properties, which dominantly affect the chromatographic lipophilicity, were determined as well. The significant correlations between the chromatographic lipophilicity and plasma protein binding (PPB), Madin-Darby Canine Kidney (MDCK) cells permeability, volume of distribution (Vd) and absorption constant (Ka) indicate the strong influence of lipophilicity on pharmacokinetics of 1-aryl-3-ethyl-3-methylsuccinimide derivatives. These derivatives have also been tested applying Comprehensive Medicinal Chemistry (CMC) drug-like rules which confirmed their drug-like properties. Besides, their blood-brain penetration (BBB) ability has been estimated applying the set of Clark's rules and by using Pre-ADMET software. Regarding toxicity, it was predicted that only one compound from the set might have toxic effects by blocking the hERG potassium channel. The present study reveals which molecular features in the structure of novel succinimide derivatives could be crucial for their lipophilicity, and consequently for their pharmacokinetic properties. The results indicate that the newly synthesized series of succinimide derivatives should be further considered in design of novel anticonvulsants.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Computational Biology and Chemistry",
title = "Chromatographic and computational screening of anisotropic lipophilicity and pharmacokinetics of newly synthesized 1-aryl-3-ethyl-3-methylsuccinimides",
volume = "84",
doi = "10.1016/j.compbiolchem.2019.107161"
}

Kovačević, S., Karadzić-Banjac, M., Podunavac-Kuzmanović, S., Milošević, N., Curcić, J., Vulić, J., Seregelj, V., Banjac, N.,& Ušćumlić, G.. (2020). Chromatographic and computational screening of anisotropic lipophilicity and pharmacokinetics of newly synthesized 1-aryl-3-ethyl-3-methylsuccinimides. in Computational Biology and Chemistry
Elsevier Sci Ltd, Oxford., 84.
https://doi.org/10.1016/j.compbiolchem.2019.107161

Kovačević S, Karadzić-Banjac M, Podunavac-Kuzmanović S, Milošević N, Curcić J, Vulić J, Seregelj V, Banjac N, Ušćumlić G. Chromatographic and computational screening of anisotropic lipophilicity and pharmacokinetics of newly synthesized 1-aryl-3-ethyl-3-methylsuccinimides. in Computational Biology and Chemistry. 2020;84.
doi:10.1016/j.compbiolchem.2019.107161 .

Kovačević, Strahinja, Karadzić-Banjac, Milica, Podunavac-Kuzmanović, Sanja, Milošević, Nataša, Curcić, Jelena, Vulić, Jelena, Seregelj, Vanja, Banjac, Nebojša, Ušćumlić, Gordana, "Chromatographic and computational screening of anisotropic lipophilicity and pharmacokinetics of newly synthesized 1-aryl-3-ethyl-3-methylsuccinimides" in Computational Biology and Chemistry, 84 (2020),
https://doi.org/10.1016/j.compbiolchem.2019.107161 . .

TY  - JOUR
AU  - Vajdle, Olga
AU  - Guzsvány, Valéria
AU  - Skorić, Dušan
AU  - Csanadi, Janos
AU  - Petković, Miloš
AU  - Avramov-Ivić, Milka
AU  - Kónya, Zoltán
AU  - Petrović, Slobodan
AU  - Bobrowski, Andrzej
PY  - 2017
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/3681
AB  - The renewable silver-amalgam film electrode (Hg(Ag)FE) was applied for voltammetric characterization and determination of semi-synthetic macrolide antibiotics azithromycin (AZI), clarithromycin (CLA) and roxithromycin (ROX) in the Britton-Robinson buffer as supporting electrolyte ranging the pH from 4.0 to 11.9. All three macrolides showed reduction signals in fairly negative potential range. During direct cathodic square wave voltammetric (SWV) investigations conducted over the potential range from -0.75 V to -2.00V vs SCE, either one or two reduction peaks were obtained in the potential range from -1.5 to -1.9 V. The shapes and intensities of the signals depend on the applied pH values in wider pH ranges. For analytical purposes concerning the development of direct cathodic SWV and adsorptive stripping SWV (SW-AdSV) methods the neutral and slightly alkaline media were suitable as pH 7.2, pH 7.4 and pH 7.0 for AZI, CIA and ROX, respectively. Based on the cyclic voltammograms recorded at these pH values, adsorption-controlled electrode kinetics process can be proposed for all three macrolides. Furthermore, the water suppressed H-1 NMR measurements in the pH range between 6.0 and 10.5 indicated that the macrolide molecules at the optimal analytical conditions are predominantly in protonated form via their tertiary amino groups which supported in all three cases their adsorption on the appropriately polarized Hg(Ag)FE electrode. The optimized direct cathodic SWV methods showed good linearity in concentration ranges 4.81-23.3 mu gmL(-1), 1.96-28.6 mu gmL(-1) and 1.48-25.9 mu gmL(-1) for AZI, CIA and ROX, respectively. The development of the SW-AdSV methods resulted in the linear responses at lower concentration ranges as 1.0-2.46 mu gmL(-1), 0.05-0.99 mu gmL(-1) and 0.10-0.99 mu gmL(-1), for AZI, CIA and ROX, respectively. The relative standard deviation for all developed methods was not higher than 1.0% except the SWV method for AZI with 4.7%. In the case of all three investigated macrolide antibiotics the protonated form of the tertiary amino group(s) at appropriate accumulation potential and time favored the adsorption of the ionic form of the target molecules offering the opportunity for the development of SW-AdSV methods for their trace level analysis on Hg(Ag)FE. Optimized SW-AdSV method was applied for determination of ROX in pharmaceutical preparation Runac.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Electrochimica Acta
T1  - Voltammetric behavior and determination of the macrolide antibiotics azithromycin, clarithromycin and roxithromycin at a renewable silver - amalgam film electrode
EP  - 344
SP  - 334
VL  - 229
DO  - 10.1016/j.electacta.2017.01.146
ER  - 

@article{
author = "Vajdle, Olga and Guzsvány, Valéria and Skorić, Dušan and Csanadi, Janos and Petković, Miloš and Avramov-Ivić, Milka and Kónya, Zoltán and Petrović, Slobodan and Bobrowski, Andrzej",
year = "2017",
abstract = "The renewable silver-amalgam film electrode (Hg(Ag)FE) was applied for voltammetric characterization and determination of semi-synthetic macrolide antibiotics azithromycin (AZI), clarithromycin (CLA) and roxithromycin (ROX) in the Britton-Robinson buffer as supporting electrolyte ranging the pH from 4.0 to 11.9. All three macrolides showed reduction signals in fairly negative potential range. During direct cathodic square wave voltammetric (SWV) investigations conducted over the potential range from -0.75 V to -2.00V vs SCE, either one or two reduction peaks were obtained in the potential range from -1.5 to -1.9 V. The shapes and intensities of the signals depend on the applied pH values in wider pH ranges. For analytical purposes concerning the development of direct cathodic SWV and adsorptive stripping SWV (SW-AdSV) methods the neutral and slightly alkaline media were suitable as pH 7.2, pH 7.4 and pH 7.0 for AZI, CIA and ROX, respectively. Based on the cyclic voltammograms recorded at these pH values, adsorption-controlled electrode kinetics process can be proposed for all three macrolides. Furthermore, the water suppressed H-1 NMR measurements in the pH range between 6.0 and 10.5 indicated that the macrolide molecules at the optimal analytical conditions are predominantly in protonated form via their tertiary amino groups which supported in all three cases their adsorption on the appropriately polarized Hg(Ag)FE electrode. The optimized direct cathodic SWV methods showed good linearity in concentration ranges 4.81-23.3 mu gmL(-1), 1.96-28.6 mu gmL(-1) and 1.48-25.9 mu gmL(-1) for AZI, CIA and ROX, respectively. The development of the SW-AdSV methods resulted in the linear responses at lower concentration ranges as 1.0-2.46 mu gmL(-1), 0.05-0.99 mu gmL(-1) and 0.10-0.99 mu gmL(-1), for AZI, CIA and ROX, respectively. The relative standard deviation for all developed methods was not higher than 1.0% except the SWV method for AZI with 4.7%. In the case of all three investigated macrolide antibiotics the protonated form of the tertiary amino group(s) at appropriate accumulation potential and time favored the adsorption of the ionic form of the target molecules offering the opportunity for the development of SW-AdSV methods for their trace level analysis on Hg(Ag)FE. Optimized SW-AdSV method was applied for determination of ROX in pharmaceutical preparation Runac.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Electrochimica Acta",
title = "Voltammetric behavior and determination of the macrolide antibiotics azithromycin, clarithromycin and roxithromycin at a renewable silver - amalgam film electrode",
pages = "344-334",
volume = "229",
doi = "10.1016/j.electacta.2017.01.146"
}

Vajdle, O., Guzsvány, V., Skorić, D., Csanadi, J., Petković, M., Avramov-Ivić, M., Kónya, Z., Petrović, S.,& Bobrowski, A.. (2017). Voltammetric behavior and determination of the macrolide antibiotics azithromycin, clarithromycin and roxithromycin at a renewable silver - amalgam film electrode. in Electrochimica Acta
Pergamon-Elsevier Science Ltd, Oxford., 229, 334-344.
https://doi.org/10.1016/j.electacta.2017.01.146

Vajdle O, Guzsvány V, Skorić D, Csanadi J, Petković M, Avramov-Ivić M, Kónya Z, Petrović S, Bobrowski A. Voltammetric behavior and determination of the macrolide antibiotics azithromycin, clarithromycin and roxithromycin at a renewable silver - amalgam film electrode. in Electrochimica Acta. 2017;229:334-344.
doi:10.1016/j.electacta.2017.01.146 .

Vajdle, Olga, Guzsvány, Valéria, Skorić, Dušan, Csanadi, Janos, Petković, Miloš, Avramov-Ivić, Milka, Kónya, Zoltán, Petrović, Slobodan, Bobrowski, Andrzej, "Voltammetric behavior and determination of the macrolide antibiotics azithromycin, clarithromycin and roxithromycin at a renewable silver - amalgam film electrode" in Electrochimica Acta, 229 (2017):334-344,
https://doi.org/10.1016/j.electacta.2017.01.146 . .

TY  - JOUR
AU  - Vajdle, Olga
AU  - Guzsvány, Valéria
AU  - Skorić, Dušan
AU  - Anojčić, Jasmina
AU  - Jovanov, Pavle
AU  - Avramov-Ivić, Milka
AU  - Csanadi, Janos
AU  - Kónya, Zoltán
AU  - Petrović, Slobodan
AU  - Bobrowski, Andrzej
PY  - 2016
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/3465
AB  - Erythromycin, a macrolide antibiotic, has similar antimicrobial spectrum to penicillin and it is widely used, especially in the treatment of patients who are allergic to penicillin. In this work, the application of a renewable silver-amalgam film electrode (Hg(Ag)FE) for the characterization and determination of erythromycin ethylsuccinate (EES), a widely used esterified form of this antibiotic, by means of cyclic voltammetry (CV) and square wave voltammetry (SWV) is presented. In the aqueous Britton-Robinson buffer (pH 5.0-9.0) that served as the supporting electrolyte, one reduction peak of EES was observed in the investigated potential range between -0.75 V and -1.80 V vs SCE, with peak potential maxima ranging from -1.59 V to -1.70 V, which strongly depended on the applied pH, as did the peak shape. For the analytical purposes the pH of 7.0 was selected, since in this electrolyte the EES peak was well-shaped and separated from the background current of the supporting electrolyte in both cases; in the direct cathodic SWV and in the case of square wave adsorptive stripping voltammetry (SW-AdSV). It was established, by the E-p-pH correlation, that protons strongly influenced the electrochemical reduction of EES. The CVs recorded between 0.025-0.50 V s (1) at pH 7.0 confirmed that the electrode reaction is adsorption-controlled. Based on the series of H-1 NMR measurements it is proved that the tertiary amino group of EES is mainly in its protonated form at pH 7.0 which may lead, at appropriate accumulation potential and time, to the favored adsorption of the target ionic form of the analyte improving on such way the sensitivity of the SW-AdSV method. The optimized procedures resulted in stable SWV responses with good linear correlation in the EES concentration range from 4.53 to 29.8 mu g mL (1) (LOD = 1.36 mu g mL (1)), and from 0.69 mu g mL (1) to 2.44 mu g mL (1) (LOD 0.21 mu g mL (1)) in the case of optimized SW-AdSV. The relative standard deviation is below 1.5%. The reliability of the elaborated procedures and thus the accuracy of the obtained results were validated by comparing them with those obtained by means of HPLC-DAD measurements. The direct cathodic SWV method was successfully applied for the determination of EES in the pharmaceutical preparation Eritromicin (R), while SW-AdSV was applied in the case of the spiked urine sample. In both cases, the standard addition method was used.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Electrochimica Acta
T1  - Voltammetric behavior of erythromycin ethylsuccinate at a renewable silver-amalgam film electrode and its determination in urine and in a pharmaceutical preparation
EP  - 54
SP  - 44
VL  - 191
DO  - 10.1016/j.electacta.2015.12.207
ER  - 

@article{
author = "Vajdle, Olga and Guzsvány, Valéria and Skorić, Dušan and Anojčić, Jasmina and Jovanov, Pavle and Avramov-Ivić, Milka and Csanadi, Janos and Kónya, Zoltán and Petrović, Slobodan and Bobrowski, Andrzej",
year = "2016",
abstract = "Erythromycin, a macrolide antibiotic, has similar antimicrobial spectrum to penicillin and it is widely used, especially in the treatment of patients who are allergic to penicillin. In this work, the application of a renewable silver-amalgam film electrode (Hg(Ag)FE) for the characterization and determination of erythromycin ethylsuccinate (EES), a widely used esterified form of this antibiotic, by means of cyclic voltammetry (CV) and square wave voltammetry (SWV) is presented. In the aqueous Britton-Robinson buffer (pH 5.0-9.0) that served as the supporting electrolyte, one reduction peak of EES was observed in the investigated potential range between -0.75 V and -1.80 V vs SCE, with peak potential maxima ranging from -1.59 V to -1.70 V, which strongly depended on the applied pH, as did the peak shape. For the analytical purposes the pH of 7.0 was selected, since in this electrolyte the EES peak was well-shaped and separated from the background current of the supporting electrolyte in both cases; in the direct cathodic SWV and in the case of square wave adsorptive stripping voltammetry (SW-AdSV). It was established, by the E-p-pH correlation, that protons strongly influenced the electrochemical reduction of EES. The CVs recorded between 0.025-0.50 V s (1) at pH 7.0 confirmed that the electrode reaction is adsorption-controlled. Based on the series of H-1 NMR measurements it is proved that the tertiary amino group of EES is mainly in its protonated form at pH 7.0 which may lead, at appropriate accumulation potential and time, to the favored adsorption of the target ionic form of the analyte improving on such way the sensitivity of the SW-AdSV method. The optimized procedures resulted in stable SWV responses with good linear correlation in the EES concentration range from 4.53 to 29.8 mu g mL (1) (LOD = 1.36 mu g mL (1)), and from 0.69 mu g mL (1) to 2.44 mu g mL (1) (LOD 0.21 mu g mL (1)) in the case of optimized SW-AdSV. The relative standard deviation is below 1.5%. The reliability of the elaborated procedures and thus the accuracy of the obtained results were validated by comparing them with those obtained by means of HPLC-DAD measurements. The direct cathodic SWV method was successfully applied for the determination of EES in the pharmaceutical preparation Eritromicin (R), while SW-AdSV was applied in the case of the spiked urine sample. In both cases, the standard addition method was used.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Electrochimica Acta",
title = "Voltammetric behavior of erythromycin ethylsuccinate at a renewable silver-amalgam film electrode and its determination in urine and in a pharmaceutical preparation",
pages = "54-44",
volume = "191",
doi = "10.1016/j.electacta.2015.12.207"
}

Vajdle, O., Guzsvány, V., Skorić, D., Anojčić, J., Jovanov, P., Avramov-Ivić, M., Csanadi, J., Kónya, Z., Petrović, S.,& Bobrowski, A.. (2016). Voltammetric behavior of erythromycin ethylsuccinate at a renewable silver-amalgam film electrode and its determination in urine and in a pharmaceutical preparation. in Electrochimica Acta
Pergamon-Elsevier Science Ltd, Oxford., 191, 44-54.
https://doi.org/10.1016/j.electacta.2015.12.207

Vajdle O, Guzsvány V, Skorić D, Anojčić J, Jovanov P, Avramov-Ivić M, Csanadi J, Kónya Z, Petrović S, Bobrowski A. Voltammetric behavior of erythromycin ethylsuccinate at a renewable silver-amalgam film electrode and its determination in urine and in a pharmaceutical preparation. in Electrochimica Acta. 2016;191:44-54.
doi:10.1016/j.electacta.2015.12.207 .

Vajdle, Olga, Guzsvány, Valéria, Skorić, Dušan, Anojčić, Jasmina, Jovanov, Pavle, Avramov-Ivić, Milka, Csanadi, Janos, Kónya, Zoltán, Petrović, Slobodan, Bobrowski, Andrzej, "Voltammetric behavior of erythromycin ethylsuccinate at a renewable silver-amalgam film electrode and its determination in urine and in a pharmaceutical preparation" in Electrochimica Acta, 191 (2016):44-54,
https://doi.org/10.1016/j.electacta.2015.12.207 . .