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, 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 . .