TY  - JOUR
AU  - Tubić, Biljana K.
AU  - Dobričić, Vladimir
AU  - Poljarević, Jelena
AU  - Savić, Aleksandar
AU  - Sabo, Tibor
AU  - Marković, Bojan D.
PY  - 2020
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3868
AB  - Passive gastrointestinal absorption and membrane retention of twelve esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP), as well as of these two non-esterified acids were estimated using PAMPA test. Artificial PAMPA membrane used in this study for the simulation of gastrointestinal barrier was solution of egg lecithin in dodecane (1 % w/v). All tested compounds belong to class III (high membrane retention and low permeation), whereas EDCP, dipentyl ester of PDCP (DPE-PDCP) and diisopentyl ester of PDCP (DIPE-PDCP) belong to class I (negligible membrane retention and low permeation). Finally, quantitative structure – permeability and structure – retention relationships models were created in order to find quantitative relationships between physico-chemical properties of tested compounds and PAMPA membrane permeability/membrane retention parameters. Statistically the most reliable models were analysed and used for the design of new compounds for which favourable membrane permeability and retention can be expected.
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives
VL  - 184
DO  - 10.1016/j.jpba.2020.113213
ER  - 

@article{
author = "Tubić, Biljana K. and Dobričić, Vladimir and Poljarević, Jelena and Savić, Aleksandar and Sabo, Tibor and Marković, Bojan D.",
year = "2020",
abstract = "Passive gastrointestinal absorption and membrane retention of twelve esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP), as well as of these two non-esterified acids were estimated using PAMPA test. Artificial PAMPA membrane used in this study for the simulation of gastrointestinal barrier was solution of egg lecithin in dodecane (1 % w/v). All tested compounds belong to class III (high membrane retention and low permeation), whereas EDCP, dipentyl ester of PDCP (DPE-PDCP) and diisopentyl ester of PDCP (DIPE-PDCP) belong to class I (negligible membrane retention and low permeation). Finally, quantitative structure – permeability and structure – retention relationships models were created in order to find quantitative relationships between physico-chemical properties of tested compounds and PAMPA membrane permeability/membrane retention parameters. Statistically the most reliable models were analysed and used for the design of new compounds for which favourable membrane permeability and retention can be expected.",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives",
volume = "184",
doi = "10.1016/j.jpba.2020.113213"
}

Tubić, B. K., Dobričić, V., Poljarević, J., Savić, A., Sabo, T.,& Marković, B. D.. (2020). Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V.., 184.
https://doi.org/10.1016/j.jpba.2020.113213

Tubić BK, Dobričić V, Poljarević J, Savić A, Sabo T, Marković BD. Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. in Journal of Pharmaceutical and Biomedical Analysis. 2020;184.
doi:10.1016/j.jpba.2020.113213 .

Tubić, Biljana K., Dobričić, Vladimir, Poljarević, Jelena, Savić, Aleksandar, Sabo, Tibor, Marković, Bojan D., "Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives" in Journal of Pharmaceutical and Biomedical Analysis, 184 (2020),
https://doi.org/10.1016/j.jpba.2020.113213 . .

TY  - CONF
AU  - Tubić, Biljana K.
AU  - Marković, Bojan D.
AU  - Sabo, Tibor
PY  - 2019
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3136
AB  - In previously in vitro studies on different cell lines and in vivo on melanoma and 4T1 murine breast cancer and metastasis it was shown antiproliferative activity for ester derivatives of (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid, and (S,S)-1,3-propanediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid. The aim of this study was to predict membrane permeability by parallel artificial membrane permeability assay (PAMPA), molecular mechanism of action, metabolites and absorption, distribution, metabolism, toxicity—ADMET properties for observed substances using in vitro and in silico methods. Obtained results of PAMPA show the best membrane permeability of ethyl esters analogs (DE-EDCP and DE-PDCP) and refer to the hypothesis that the retention in cell membrane is important for cytotoxic activity of investigated substances. Prediction of main metabolic pathways was performed by the Metabolizer software and it was obtained that the major metabolic reactions were the hydrolyses of ester and subsequently intramolecular cyclization. Toxicity of investigated substances and their potential metabolites are lower than toxicity of observed official cytotoxic drugs. Based on the results obtained by the Molecular docking, it can be assumed that the antiproliferative effects of the investigated substances were realized through the multiple mechanisms by potential metabolites: acids, lactam carboxylate and lactam alkyl esters, while the esters are probably a prodrug substance with favorable properties to provide sufficient bioavailability at the target of action. Based on obtained results it can be proposed there to be investigated the existence of the metabolites: lactam carboxylate and lactam alkyl esters in biological materials.
C3  - IFMBE Proceedings
T1  - Discovery of membrane permeability, pharmacokinetics properties and mechanism of action for analogs of ethylenediamine-n,n′-di-2-(3-cyclohexyl)propionic acid and 1,3-propandiamine-n,n′-di-2-(3-cyclohexyl)propionic acid with antiproliferative activity using in vitro and in silico methods
VL  - 73
SP  - 357
EP  - 369
DO  - 10.1007/978-3-030-17971-7_55
ER  - 

@conference{
author = "Tubić, Biljana K. and Marković, Bojan D. and Sabo, Tibor",
year = "2019",
abstract = "In previously in vitro studies on different cell lines and in vivo on melanoma and 4T1 murine breast cancer and metastasis it was shown antiproliferative activity for ester derivatives of (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid, and (S,S)-1,3-propanediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid. The aim of this study was to predict membrane permeability by parallel artificial membrane permeability assay (PAMPA), molecular mechanism of action, metabolites and absorption, distribution, metabolism, toxicity—ADMET properties for observed substances using in vitro and in silico methods. Obtained results of PAMPA show the best membrane permeability of ethyl esters analogs (DE-EDCP and DE-PDCP) and refer to the hypothesis that the retention in cell membrane is important for cytotoxic activity of investigated substances. Prediction of main metabolic pathways was performed by the Metabolizer software and it was obtained that the major metabolic reactions were the hydrolyses of ester and subsequently intramolecular cyclization. Toxicity of investigated substances and their potential metabolites are lower than toxicity of observed official cytotoxic drugs. Based on the results obtained by the Molecular docking, it can be assumed that the antiproliferative effects of the investigated substances were realized through the multiple mechanisms by potential metabolites: acids, lactam carboxylate and lactam alkyl esters, while the esters are probably a prodrug substance with favorable properties to provide sufficient bioavailability at the target of action. Based on obtained results it can be proposed there to be investigated the existence of the metabolites: lactam carboxylate and lactam alkyl esters in biological materials.",
journal = "IFMBE Proceedings",
title = "Discovery of membrane permeability, pharmacokinetics properties and mechanism of action for analogs of ethylenediamine-n,n′-di-2-(3-cyclohexyl)propionic acid and 1,3-propandiamine-n,n′-di-2-(3-cyclohexyl)propionic acid with antiproliferative activity using in vitro and in silico methods",
volume = "73",
pages = "357-369",
doi = "10.1007/978-3-030-17971-7_55"
}

Tubić, B. K., Marković, B. D.,& Sabo, T.. (2019). Discovery of membrane permeability, pharmacokinetics properties and mechanism of action for analogs of ethylenediamine-n,n′-di-2-(3-cyclohexyl)propionic acid and 1,3-propandiamine-n,n′-di-2-(3-cyclohexyl)propionic acid with antiproliferative activity using in vitro and in silico methods. in IFMBE Proceedings, 73, 357-369.
https://doi.org/10.1007/978-3-030-17971-7_55

Tubić BK, Marković BD, Sabo T. Discovery of membrane permeability, pharmacokinetics properties and mechanism of action for analogs of ethylenediamine-n,n′-di-2-(3-cyclohexyl)propionic acid and 1,3-propandiamine-n,n′-di-2-(3-cyclohexyl)propionic acid with antiproliferative activity using in vitro and in silico methods. in IFMBE Proceedings. 2019;73:357-369.
doi:10.1007/978-3-030-17971-7_55 .

Tubić, Biljana K., Marković, Bojan D., Sabo, Tibor, "Discovery of membrane permeability, pharmacokinetics properties and mechanism of action for analogs of ethylenediamine-n,n′-di-2-(3-cyclohexyl)propionic acid and 1,3-propandiamine-n,n′-di-2-(3-cyclohexyl)propionic acid with antiproliferative activity using in vitro and in silico methods" in IFMBE Proceedings, 73 (2019):357-369,
https://doi.org/10.1007/978-3-030-17971-7_55 . .

TY  - JOUR
AU  - Tubić, Biljana K.
AU  - Vladimirov, Sandra S.
AU  - Marković, Bojan D.
AU  - Sabo, Tibor
PY  - 2018
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2113
AB  - O,O'-diethyl-(S, S)-ethylenediamine-N, N'-di-2-(3-cyclohexyl) propanoate (DE-EDCP) is novel substance with cytotoxic activity in human leukemic cells. The aim of this study has been to predict in vivo bioavailability of the DE-EDCP and its potential metabolite (S, S)-ethylenediamine-N, N'-di-2-(3-cyclohexyl) propanoic acid (EDCP) by in vitro characterization which includes determination of lipophilicity and passive membrane permeability. There has also been evaluated inter-laboratory reproducibility of the bio-analytical method which was previously developed and validated for non-clinical study of the DE-EDCP and EDCP. Distribution coefficient n-octanol/water was 1.68 and 0.03, and apparent permeability coefficient was 4 x 10(-4) cm/s and 20 x 10(-4) cm/s, for the DE-EDCP and EDCP, respectively. Observed results have shown that the DE-EDCP is more lipophilic with better membrane retention, but the EDCP has better pass through the membrane. Also, there has been demonstrated a reproducibility and robustness of the proposed bio-analytical method.
PB  - Slovensko Kemijsko Drustvo, Ljubljana
T2  - Acta Chimica Slovenica
T1  - Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity
VL  - 65
IS  - 1
SP  - 59
EP  - 64
DO  - 10.17344/acsi.2017.3477
ER  - 

@article{
author = "Tubić, Biljana K. and Vladimirov, Sandra S. and Marković, Bojan D. and Sabo, Tibor",
year = "2018",
abstract = "O,O'-diethyl-(S, S)-ethylenediamine-N, N'-di-2-(3-cyclohexyl) propanoate (DE-EDCP) is novel substance with cytotoxic activity in human leukemic cells. The aim of this study has been to predict in vivo bioavailability of the DE-EDCP and its potential metabolite (S, S)-ethylenediamine-N, N'-di-2-(3-cyclohexyl) propanoic acid (EDCP) by in vitro characterization which includes determination of lipophilicity and passive membrane permeability. There has also been evaluated inter-laboratory reproducibility of the bio-analytical method which was previously developed and validated for non-clinical study of the DE-EDCP and EDCP. Distribution coefficient n-octanol/water was 1.68 and 0.03, and apparent permeability coefficient was 4 x 10(-4) cm/s and 20 x 10(-4) cm/s, for the DE-EDCP and EDCP, respectively. Observed results have shown that the DE-EDCP is more lipophilic with better membrane retention, but the EDCP has better pass through the membrane. Also, there has been demonstrated a reproducibility and robustness of the proposed bio-analytical method.",
publisher = "Slovensko Kemijsko Drustvo, Ljubljana",
journal = "Acta Chimica Slovenica",
title = "Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity",
volume = "65",
number = "1",
pages = "59-64",
doi = "10.17344/acsi.2017.3477"
}

Tubić, B. K., Vladimirov, S. S., Marković, B. D.,& Sabo, T.. (2018). Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity. in Acta Chimica Slovenica
Slovensko Kemijsko Drustvo, Ljubljana., 65(1), 59-64.
https://doi.org/10.17344/acsi.2017.3477

Tubić BK, Vladimirov SS, Marković BD, Sabo T. Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity. in Acta Chimica Slovenica. 2018;65(1):59-64.
doi:10.17344/acsi.2017.3477 .

Tubić, Biljana K., Vladimirov, Sandra S., Marković, Bojan D., Sabo, Tibor, "Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity" in Acta Chimica Slovenica, 65, no. 1 (2018):59-64,
https://doi.org/10.17344/acsi.2017.3477 . .

TY  - CONF
AU  - Tubić, Biljana K.
AU  - Marković, Bojan D.
AU  - Vladimirov, S.
AU  - Savić, Aleksandar
AU  - Poljarević, Jelena
AU  - Sabo, Tibor
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/307
AB  - During the early stages of drug discovery, it is very important to determine lipophilicity and to investigate and predict processes of drug distribution and resorption in human body, i.e. their bioavailability. Novel fourteen compounds representing ester derivatives of (S,S')-1,2- ethanediamme-N,N'-di-2-(3-cyclohexyl)propanoic and (S,S)- 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acids, expressing antiproliferative activity in vitro were examined. The objective of this study was to estimation a lipophilicity data of observed fourteen compounds by ultra-high performance liquid chromatographic tandem mass spectrometry (UHPLC-MS) method. It was used gradient and isocratic method to obtain chromatographic parameters of lipophilicity/ hydrophobicity, which are needed for calculated logP values. Results of lipophilicity data for observed 14 compounds, which were obtained by UHPLC-MS method and presented in this paper, are showed that the derivatives of 1,2 ethandiamine-N,N'-di-2-(3-cyclohexyl) propanoic acid have higer values of logP, than derivatives of 1,3-propanediamine- N,N'-di-2-(3-cyclohexyl) propanoic acid. Also, value of lipophilicity data for each of investigated compounds depends on the length of the alkyl chain on the esters bounds. Branching of the alkyl chain on the esters bounds has insignificant influence on the values of lipophilicity/ hydrophobicity.
PB  - Springer Nature Singapore Pte Ltd.
C3  - IFMBE Proceedings
T1  - Estimation of lipophilicity data for derivatives of alkandiamine-N,N’-di-2-(3-cyclohexyl) propanoic acid with potential antineoplastic activity, by UHPLC-MS method
VL  - 62
SP  - 402
EP  - 409
DO  - 10.1007/978-981-10-4166-2_62
ER  - 

@conference{
author = "Tubić, Biljana K. and Marković, Bojan D. and Vladimirov, S. and Savić, Aleksandar and Poljarević, Jelena and Sabo, Tibor",
year = "2017",
abstract = "During the early stages of drug discovery, it is very important to determine lipophilicity and to investigate and predict processes of drug distribution and resorption in human body, i.e. their bioavailability. Novel fourteen compounds representing ester derivatives of (S,S')-1,2- ethanediamme-N,N'-di-2-(3-cyclohexyl)propanoic and (S,S)- 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acids, expressing antiproliferative activity in vitro were examined. The objective of this study was to estimation a lipophilicity data of observed fourteen compounds by ultra-high performance liquid chromatographic tandem mass spectrometry (UHPLC-MS) method. It was used gradient and isocratic method to obtain chromatographic parameters of lipophilicity/ hydrophobicity, which are needed for calculated logP values. Results of lipophilicity data for observed 14 compounds, which were obtained by UHPLC-MS method and presented in this paper, are showed that the derivatives of 1,2 ethandiamine-N,N'-di-2-(3-cyclohexyl) propanoic acid have higer values of logP, than derivatives of 1,3-propanediamine- N,N'-di-2-(3-cyclohexyl) propanoic acid. Also, value of lipophilicity data for each of investigated compounds depends on the length of the alkyl chain on the esters bounds. Branching of the alkyl chain on the esters bounds has insignificant influence on the values of lipophilicity/ hydrophobicity.",
publisher = "Springer Nature Singapore Pte Ltd.",
journal = "IFMBE Proceedings",
title = "Estimation of lipophilicity data for derivatives of alkandiamine-N,N’-di-2-(3-cyclohexyl) propanoic acid with potential antineoplastic activity, by UHPLC-MS method",
volume = "62",
pages = "402-409",
doi = "10.1007/978-981-10-4166-2_62"
}

Tubić, B. K., Marković, B. D., Vladimirov, S., Savić, A., Poljarević, J.,& Sabo, T.. (2017). Estimation of lipophilicity data for derivatives of alkandiamine-N,N’-di-2-(3-cyclohexyl) propanoic acid with potential antineoplastic activity, by UHPLC-MS method. in IFMBE Proceedings
Springer Nature Singapore Pte Ltd.., 62, 402-409.
https://doi.org/10.1007/978-981-10-4166-2_62

Tubić BK, Marković BD, Vladimirov S, Savić A, Poljarević J, Sabo T. Estimation of lipophilicity data for derivatives of alkandiamine-N,N’-di-2-(3-cyclohexyl) propanoic acid with potential antineoplastic activity, by UHPLC-MS method. in IFMBE Proceedings. 2017;62:402-409.
doi:10.1007/978-981-10-4166-2_62 .

Tubić, Biljana K., Marković, Bojan D., Vladimirov, S., Savić, Aleksandar, Poljarević, Jelena, Sabo, Tibor, "Estimation of lipophilicity data for derivatives of alkandiamine-N,N’-di-2-(3-cyclohexyl) propanoic acid with potential antineoplastic activity, by UHPLC-MS method" in IFMBE Proceedings, 62 (2017):402-409,
https://doi.org/10.1007/978-981-10-4166-2_62 . .

TY  - JOUR
AU  - Tubić, Biljana K.
AU  - Marković, Bojan D.
AU  - Vladimirov, Sandra S.
AU  - Ristić, Slavica M.
AU  - Ivković, Branka
AU  - Savić, Miroslav M.
AU  - Poljarević, Jelena
AU  - Sabo, Tibor
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2459
AB  - A series of new (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (LOQ) was 1.3 ng mL(-1) for DE-EDCP and 0.3 mu g mL(-1) for EDCP. The calibration curves were linear over the concentration range of 1.3-26.7 ng mL(-1) and 0.3-6.7 mu g mL(-1) for DE-EDCP and EDCP, respectively. Precision (%CV) and accuracy (% RE) for DE-EDCP and EDCP ranged from 3.5% to 16.0% and from 1.8% to 14.4%, respectively. The validation process was performed in accordance with the regulatory guidance/guideline, and all of the obtained results met the established acceptance criteria. The newly developed and validated UHPLC-MS/MS method is rapid, sensitive, and selective, and it can be successfully applied to drug monitoring in nonclinical studies.
PB  - Akademiai Kiado Rt, Budapest
T2  - Acta Chromatographica
T1  - Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum
VL  - 29
IS  - 2
SP  - 235
EP  - 252
DO  - 10.1556/1326.2017.29.2.7
ER  - 

@article{
author = "Tubić, Biljana K. and Marković, Bojan D. and Vladimirov, Sandra S. and Ristić, Slavica M. and Ivković, Branka and Savić, Miroslav M. and Poljarević, Jelena and Sabo, Tibor",
year = "2017",
abstract = "A series of new (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (LOQ) was 1.3 ng mL(-1) for DE-EDCP and 0.3 mu g mL(-1) for EDCP. The calibration curves were linear over the concentration range of 1.3-26.7 ng mL(-1) and 0.3-6.7 mu g mL(-1) for DE-EDCP and EDCP, respectively. Precision (%CV) and accuracy (% RE) for DE-EDCP and EDCP ranged from 3.5% to 16.0% and from 1.8% to 14.4%, respectively. The validation process was performed in accordance with the regulatory guidance/guideline, and all of the obtained results met the established acceptance criteria. The newly developed and validated UHPLC-MS/MS method is rapid, sensitive, and selective, and it can be successfully applied to drug monitoring in nonclinical studies.",
publisher = "Akademiai Kiado Rt, Budapest",
journal = "Acta Chromatographica",
title = "Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum",
volume = "29",
number = "2",
pages = "235-252",
doi = "10.1556/1326.2017.29.2.7"
}

Tubić, B. K., Marković, B. D., Vladimirov, S. S., Ristić, S. M., Ivković, B., Savić, M. M., Poljarević, J.,& Sabo, T.. (2017). Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum. in Acta Chromatographica
Akademiai Kiado Rt, Budapest., 29(2), 235-252.
https://doi.org/10.1556/1326.2017.29.2.7

Tubić BK, Marković BD, Vladimirov SS, Ristić SM, Ivković B, Savić MM, Poljarević J, Sabo T. Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum. in Acta Chromatographica. 2017;29(2):235-252.
doi:10.1556/1326.2017.29.2.7 .

Tubić, Biljana K., Marković, Bojan D., Vladimirov, Sandra S., Ristić, Slavica M., Ivković, Branka, Savić, Miroslav M., Poljarević, Jelena, Sabo, Tibor, "Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum" in Acta Chromatographica, 29, no. 2 (2017):235-252,
https://doi.org/10.1556/1326.2017.29.2.7 . .

TY  - JOUR
AU  - Tubić, Biljana K.
AU  - Marković, Bojan D.
AU  - Vladimirov, S.
AU  - Savic, S.
AU  - Poljarević, Jelena
AU  - Sabo, Tibor
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2499
AB  - Fourteen compounds representing ester derivatives of (S,S)-1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl) propanoic and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acids, expressing antiproliferative activity in vitro were examined. The objective of this study was to determinate their lipophilicity data, and also to ensure a mathematical model for prediction lipophilicity data of potential in vivo metabolites and new derivatives of (S,S)-1,2-ethanediannine-N,N'-di-2-(3-cyclohexyl)propanoic acid, based on chromatographic parameters. Experimentally, lipophilicity data were obtained by a traditional shake flask procedure and an ultra-high performance liquid chromatographic tandem mass spectrometry (UHPLC-MS) method. A correlation between the partition coefficient n-octanol/water (logD(7,4)) and chromatographic data (CHI, phi(0)), and also, between logD(7,4) and retention time was investigated. A very good correlation (r(2)=0.8969) was found between lipophilicity parameters phi(0) and logD(7,4) obtained using UHPLC-MS and shake flask methods: logD(7,4) = (0.11 +/- 0.01)x phi(0) + (1.25 +/- 0.20)xN(c) - (9.19 +/- 1.18); statistical parameter F=47.84; significance of F = 3.74x10(-6), N-c=number of C atoms between two amino groups (N-c=2 for 1,2-ethanediamine derivatives and N-c=3 for 1,3-propanediamine derivatives).The model predictivity power was determined by cross validation leave one out (LOO) technique, and expressed by the term Q(2), was 0.89. The developed model has good predictivity power for prediction lipophilicity data of potential in vivo metabolites of the investigated compounds, such as novel 1,2-ethanediamine and 1,3-propanediamine N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. Also, the lipophilicity data obtained in the present study correlated with the antiproliferative activity of the investigated substances shown previously in in vitro studies.
PB  - Govi-Verlag  Pharmazeutischer Verlag Gmbh, Eschborn
T2  - Pharmazie
T1  - A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me
VL  - 72
IS  - 6
SP  - 317
EP  - 323
DO  - 10.1619/ph.2017.6208
ER  - 

@article{
author = "Tubić, Biljana K. and Marković, Bojan D. and Vladimirov, S. and Savic, S. and Poljarević, Jelena and Sabo, Tibor",
year = "2017",
abstract = "Fourteen compounds representing ester derivatives of (S,S)-1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl) propanoic and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acids, expressing antiproliferative activity in vitro were examined. The objective of this study was to determinate their lipophilicity data, and also to ensure a mathematical model for prediction lipophilicity data of potential in vivo metabolites and new derivatives of (S,S)-1,2-ethanediannine-N,N'-di-2-(3-cyclohexyl)propanoic acid, based on chromatographic parameters. Experimentally, lipophilicity data were obtained by a traditional shake flask procedure and an ultra-high performance liquid chromatographic tandem mass spectrometry (UHPLC-MS) method. A correlation between the partition coefficient n-octanol/water (logD(7,4)) and chromatographic data (CHI, phi(0)), and also, between logD(7,4) and retention time was investigated. A very good correlation (r(2)=0.8969) was found between lipophilicity parameters phi(0) and logD(7,4) obtained using UHPLC-MS and shake flask methods: logD(7,4) = (0.11 +/- 0.01)x phi(0) + (1.25 +/- 0.20)xN(c) - (9.19 +/- 1.18); statistical parameter F=47.84; significance of F = 3.74x10(-6), N-c=number of C atoms between two amino groups (N-c=2 for 1,2-ethanediamine derivatives and N-c=3 for 1,3-propanediamine derivatives).The model predictivity power was determined by cross validation leave one out (LOO) technique, and expressed by the term Q(2), was 0.89. The developed model has good predictivity power for prediction lipophilicity data of potential in vivo metabolites of the investigated compounds, such as novel 1,2-ethanediamine and 1,3-propanediamine N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. Also, the lipophilicity data obtained in the present study correlated with the antiproliferative activity of the investigated substances shown previously in in vitro studies.",
publisher = "Govi-Verlag  Pharmazeutischer Verlag Gmbh, Eschborn",
journal = "Pharmazie",
title = "A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me",
volume = "72",
number = "6",
pages = "317-323",
doi = "10.1619/ph.2017.6208"
}

Tubić, B. K., Marković, B. D., Vladimirov, S., Savic, S., Poljarević, J.,& Sabo, T.. (2017). A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me. in Pharmazie
Govi-Verlag  Pharmazeutischer Verlag Gmbh, Eschborn., 72(6), 317-323.
https://doi.org/10.1619/ph.2017.6208

Tubić BK, Marković BD, Vladimirov S, Savic S, Poljarević J, Sabo T. A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me. in Pharmazie. 2017;72(6):317-323.
doi:10.1619/ph.2017.6208 .

Tubić, Biljana K., Marković, Bojan D., Vladimirov, S., Savic, S., Poljarević, Jelena, Sabo, Tibor, "A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me" in Pharmazie, 72, no. 6 (2017):317-323,
https://doi.org/10.1619/ph.2017.6208 . .

TY  - JOUR
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
AU  - Vujčić, Zoran
AU  - Marković, Bojan D.
AU  - Vasiljević, Dragana
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2349
AB  - A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C-18 Analytical, 4.6 x 100 mm (3.5 mu m) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 mu L min(-1). The column was kept at constant temperature (25 degrees C), and autosampler tray temperature was set at 4 degrees C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 - gt  Q3, collision energy) atorvastatin (559.47 - gt  440.03, 22 eV), atorvastatin lactone (541.36 - gt  448.02, 19 eV), orthohydroxyatorvastatin (575.20 - gt  440.18, 20 eV), para-hydroxyatorvastatin (575.54 - gt  440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5-20 ng mL(-1) for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1-20 ng mL(-1) for atorvastatin and atorvastatin lactone with excellent linearity (r(2)  gt = 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL(-1) for orthohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL(-1) for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.
PB  - Akademiai Kiado Rt, Budapest
T2  - Acta Chromatographica
T1  - LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma
VL  - 28
IS  - 3
SP  - 281
EP  - 298
DO  - 10.1556/1326.2016.28.3.1
ER  - 

@article{
author = "Crevar-Sakač, Milkica and Vujić, Zorica and Vujčić, Zoran and Marković, Bojan D. and Vasiljević, Dragana",
year = "2016",
abstract = "A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C-18 Analytical, 4.6 x 100 mm (3.5 mu m) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 mu L min(-1). The column was kept at constant temperature (25 degrees C), and autosampler tray temperature was set at 4 degrees C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 - gt  Q3, collision energy) atorvastatin (559.47 - gt  440.03, 22 eV), atorvastatin lactone (541.36 - gt  448.02, 19 eV), orthohydroxyatorvastatin (575.20 - gt  440.18, 20 eV), para-hydroxyatorvastatin (575.54 - gt  440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5-20 ng mL(-1) for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1-20 ng mL(-1) for atorvastatin and atorvastatin lactone with excellent linearity (r(2)  gt = 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL(-1) for orthohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL(-1) for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.",
publisher = "Akademiai Kiado Rt, Budapest",
journal = "Acta Chromatographica",
title = "LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma",
volume = "28",
number = "3",
pages = "281-298",
doi = "10.1556/1326.2016.28.3.1"
}

Crevar-Sakač, M., Vujić, Z., Vujčić, Z., Marković, B. D.,& Vasiljević, D.. (2016). LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma. in Acta Chromatographica
Akademiai Kiado Rt, Budapest., 28(3), 281-298.
https://doi.org/10.1556/1326.2016.28.3.1

Crevar-Sakač M, Vujić Z, Vujčić Z, Marković BD, Vasiljević D. LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma. in Acta Chromatographica. 2016;28(3):281-298.
doi:10.1556/1326.2016.28.3.1 .

Crevar-Sakač, Milkica, Vujić, Zorica, Vujčić, Zoran, Marković, Bojan D., Vasiljević, Dragana, "LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma" in Acta Chromatographica, 28, no. 3 (2016):281-298,
https://doi.org/10.1556/1326.2016.28.3.1 . .

TY  - JOUR
AU  - Sokić, M.
AU  - Kamberović, Željko
AU  - Nikolić, Vladimir
AU  - Marković, Bojan D.
AU  - Korać, Marija
AU  - Anić, Z.
AU  - Gavrilovski, Milorad
PY  - 2015
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/287
AB  - The objects of this investigation were the comparative kinetic analysis of the NiO and NiCl2 reduction by hydrogen during an induction period and elimination of the calcination during the synthesis of Ni/Al2O3 catalysts. The effect of temperature and time on NiO and NiCl2 reduction degrees was studied. Avrami I equation was selected as the most favorable kinetic model and used to determine activation energy of the NiO and NiCl2 reduction for the investigated temperature range (623-923 K) and time intervals (1-5 minutes). The investigation enabled reaching conclusions about the reaction ability and rate of the reduction processes. Afterward, Ni/Al2O3 catalysts were obtained by using oxide and chloride precursor for Ni. The catalysts were supported on alumina-based foam and prepared via aerosol route. Properties of the samples before and after low-temperature hydrogen reduction (633 K) were compared. Obtained results indicated that the synthesis of Ni/Al2O3 catalysts can be more efficient if chloride precursor for Ni is directly reduced by hydrogen during the synthesis process, without the calcination step. In addition, Ni-Pd/Al2O3 catalysts with different metal content were prepared by using chloride precursors. Lower reduction temperature was utilized and the chlorides were almost completely reduced at 533 K. © 2015 Miroslav Sokić et al.
T2  - Scientific World Journal
T1  - Kinetics of NiO and NiCl2 hydrogen reduction as precursors and properties of produced Ni/Al2O3 and Ni-Pd/Al2O3 catalysts
VL  - 2015
SP  - 601970
DO  - 10.1155/2015/601970
ER  - 

@article{
author = "Sokić, M. and Kamberović, Željko and Nikolić, Vladimir and Marković, Bojan D. and Korać, Marija and Anić, Z. and Gavrilovski, Milorad",
year = "2015",
abstract = "The objects of this investigation were the comparative kinetic analysis of the NiO and NiCl2 reduction by hydrogen during an induction period and elimination of the calcination during the synthesis of Ni/Al2O3 catalysts. The effect of temperature and time on NiO and NiCl2 reduction degrees was studied. Avrami I equation was selected as the most favorable kinetic model and used to determine activation energy of the NiO and NiCl2 reduction for the investigated temperature range (623-923 K) and time intervals (1-5 minutes). The investigation enabled reaching conclusions about the reaction ability and rate of the reduction processes. Afterward, Ni/Al2O3 catalysts were obtained by using oxide and chloride precursor for Ni. The catalysts were supported on alumina-based foam and prepared via aerosol route. Properties of the samples before and after low-temperature hydrogen reduction (633 K) were compared. Obtained results indicated that the synthesis of Ni/Al2O3 catalysts can be more efficient if chloride precursor for Ni is directly reduced by hydrogen during the synthesis process, without the calcination step. In addition, Ni-Pd/Al2O3 catalysts with different metal content were prepared by using chloride precursors. Lower reduction temperature was utilized and the chlorides were almost completely reduced at 533 K. © 2015 Miroslav Sokić et al.",
journal = "Scientific World Journal",
title = "Kinetics of NiO and NiCl2 hydrogen reduction as precursors and properties of produced Ni/Al2O3 and Ni-Pd/Al2O3 catalysts",
volume = "2015",
pages = "601970",
doi = "10.1155/2015/601970"
}

Sokić, M., Kamberović, Ž., Nikolić, V., Marković, B. D., Korać, M., Anić, Z.,& Gavrilovski, M.. (2015). Kinetics of NiO and NiCl2 hydrogen reduction as precursors and properties of produced Ni/Al2O3 and Ni-Pd/Al2O3 catalysts. in Scientific World Journal, 2015, 601970.
https://doi.org/10.1155/2015/601970

Sokić M, Kamberović Ž, Nikolić V, Marković BD, Korać M, Anić Z, Gavrilovski M. Kinetics of NiO and NiCl2 hydrogen reduction as precursors and properties of produced Ni/Al2O3 and Ni-Pd/Al2O3 catalysts. in Scientific World Journal. 2015;2015:601970.
doi:10.1155/2015/601970 .

Sokić, M., Kamberović, Željko, Nikolić, Vladimir, Marković, Bojan D., Korać, Marija, Anić, Z., Gavrilovski, Milorad, "Kinetics of NiO and NiCl2 hydrogen reduction as precursors and properties of produced Ni/Al2O3 and Ni-Pd/Al2O3 catalysts" in Scientific World Journal, 2015 (2015):601970,
https://doi.org/10.1155/2015/601970 . .