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
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2017
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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.
Izvor:
Pharmazie, 2017, 72, 6, 317-323Izdavač:
- Govi-Verlag Pharmazeutischer Verlag Gmbh, Eschborn
Finansiranje / projekti:
- Razvoj molekula sa antiinflamatornim i kardioproaktivnim dejstvom: strukturne modifikacije, modelovanje, fizičkohemijska karakterizacija i formulaciona ispitivanja (RS-MESTD-Basic Research (BR or ON)-172041)
DOI: 10.1619/ph.2017.6208
ISSN: 0031-7144
PubMed: 29442018
WoS: 000406990300003
Scopus: 2-s2.0-85020316640
Institucija/grupa
PharmacyTY - JOUR AU - Tubić, Biljana AU - Marković, Bojan AU - Vladimirov, S. AU - Savić, Snežana AU - Poljarević, Jelena AU - Sabo, Tibor PY - 2017 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2796 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 and Marković, Bojan and Vladimirov, S. and Savić, Snežana 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., Marković, B., Vladimirov, S., Savić, 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 B, Marković B, Vladimirov S, Savić 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, Marković, Bojan, Vladimirov, S., Savić, Snežana, 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 . .